Immunotherapy with Cleavage-Specific 12A12mAb Reduces the Tau Cleavage in Visual Cortex and Improves Visuo-Spatial Recognition Memory in Tg2576 AD Mouse Model

Tau-targeted immunotherapy is a promising approach for treatment of Alzheimer’s disease (AD). Beyond cognitive decline, AD features visual deficits consistent with the manifestation of Amyloid β-protein (Aβ) plaques and neurofibrillary tangles (NFT) in the eyes and higher visual centers, both in animal models and affected subjects. We reported that 12A12—a monoclonal cleavage-specific antibody (mAb) which in vivo neutralizes the neurotoxic, N-terminal 20–22 kDa tau fragment(s)–significantly reduces the retinal accumulation in Tg(HuAPP695Swe)2576 mice of both tau and APP/Aβ pathologies correlated with local inflammation and synaptic deterioration. Here, we report the occurrence of N-terminal tau cleavage in the primary visual cortex (V1 area) and the beneficial effect of 12A12mAb treatment on phenotype-associated visuo-spatial deficits in this AD animal model. We found out that non-invasive administration of 12 A12mAb markedly reduced the pathological accumulation of both truncated tau and Aβ in the V1 area, correlated to significant improvement in visual recognition memory performance along with local increase in two direct readouts of cortical synaptic plasticity, including the dendritic spine density and the expression level of activity-regulated cytoskeleton protein Arc/Arg3.1. Translation of these findings to clinical therapeutic interventions could offer an innovative tau-directed opportunity to delay or halt the visual impairments occurring during AD progression

[1]  S. Picaud,et al.  Dysfunction of the glutamatergic photoreceptor synapse in the P301S mouse model of tauopathy , 2023, Acta Neuropathologica Communications.

[2]  S. Qiu,et al.  Early impairment of cortical circuit plasticity and connectivity in the 5XFAD Alzheimer’s disease mouse model , 2022, Translational Psychiatry.

[3]  J Zhang,et al.  The retina: A window in which to view the pathogenesis of Alzheimer’s disease , 2022, Ageing Research Reviews.

[4]  Fabio R. Rodrigues,et al.  Plasticity in visual cortex is disrupted in a mouse model of tauopathy , 2020, Communications Biology.

[5]  R. Gămănuţ,et al.  Anatomical and functional connectomes underlying hierarchical visual processing in mouse visual system , 2021, Brain Structure and Function.

[6]  J. Bamburg,et al.  Cofilin and Actin Dynamics: Multiple Modes of Regulation and Their Impacts in Neuronal Development and Degeneration , 2021, Cells.

[7]  B. Marwick,et al.  Ophthalmic Biomarkers for Alzheimer’s Disease: A Review , 2021, Frontiers in Aging Neuroscience.

[8]  A. Pascale,et al.  Ocular Neurodegenerative Diseases: Interconnection between Retina and Cortical Areas , 2021, Cells.

[9]  Natalie D. Phillips,et al.  Visual Performance and Cortical Atrophy in Vision-Related Brain Regions Differ Between Older Adults with (or at Risk for) Alzheimer's Disease. , 2021, Journal of Alzheimer's disease : JAD.

[10]  N. Ip,et al.  Retinal Dysfunction in Alzheimer’s Disease and Implications for Biomarkers , 2021, Biomolecules.

[11]  David C. Zhu,et al.  Alzheimer’s Disease Progressively Reduces Visual Functional Network Connectivity , 2021, Journal of Alzheimer's disease reports.

[12]  L. Tan,et al.  Retinal biomarkers in Alzheimer’s disease and mild cognitive impairment: A systematic review and meta-analysis , 2021, Ageing Research Reviews.

[13]  M. Cordeiro,et al.  Retinal Changes in Transgenic Mouse Models of Alzheimer's Disease. , 2021, Current Alzheimer research.

[14]  B. Hyman,et al.  Impairment of visual cortical plasticity by amyloid-beta species , 2021, Neurobiology of Disease.

[15]  M. Varano,et al.  Systemic delivery of a specific antibody targeting the pathological N-terminal truncated tau peptide reduces retinal degeneration in a mouse model of Alzheimer’s Disease , 2021, Acta neuropathologica communications.

[16]  Cecilia S Lee,et al.  Understanding the Brain through Aging Eyes , 2021, Advances in geriatric medicine and research.

[17]  M. Duncan,et al.  A simple method for quantitating confocal fluorescent images , 2021, Biochemistry and biophysics reports.

[18]  K. Black,et al.  Color and contrast vision in mouse models of aging and Alzheimer’s disease using a novel visual-stimuli four-arm maze , 2021, Scientific Reports.

[19]  Jeremiah K. H. Lim,et al.  Retinal changes in Alzheimer's disease— integrated prospects of imaging, functional and molecular advances , 2020, Progress in Retinal and Eye Research.

[20]  Pete A. Williams,et al.  Retinal ganglion cell degeneration correlates with hippocampal spine loss in experimental Alzheimer’s disease , 2020, Acta neuropathologica communications.

[21]  Wei Yuan,et al.  Role of Cofilin in Alzheimer’s Disease , 2020, Frontiers in Cell and Developmental Biology.

[22]  Zhengping Jia,et al.  The Role of ADF/Cofilin in Synaptic Physiology and Alzheimer’s Disease , 2020, Frontiers in Cell and Developmental Biology.

[23]  M. Castelo‐Branco,et al.  The Retinal Inner Plexiform Synaptic Layer Mirrors Grey Matter Thickness of Primary Visual Cortex with Increased Amyloid β Load in Early Alzheimer's Disease , 2020, Neural plasticity.

[24]  K. Black,et al.  Alzheimer’s Retinopathy: Seeing Disease in the Eyes , 2020, Frontiers in Neuroscience.

[25]  David C. Zhu,et al.  Alzheimer's Disease Progressively Alters the Face-Evoked Visual-Processing Network. , 2020, Journal of Alzheimer's disease : JAD.

[26]  F. Lopera,et al.  Association Between Visual Memory and In Vivo Amyloid and Tau Pathology in Preclinical Autosomal Dominant Alzheimer’s Disease , 2020, Journal of the International Neuropsychological Society.

[27]  S. Joly,et al.  Tau modulates visual plasticity in adult and old mice , 2020, Neurobiology of Aging.

[28]  Keith A. Johnson,et al.  Visual short-term memory relates to tau and amyloid burdens in preclinical autosomal dominant Alzheimer’s disease , 2020, Alzheimer's Research & Therapy.

[29]  B. Franco,et al.  α-synuclein overexpression in the retina leads to vision impairment and degeneration of dopaminergic amacrine cells , 2020, Scientific Reports.

[30]  K. Na,et al.  Low vision and the risk of dementia: a nationwide population-based cohort study , 2020, Scientific Reports.

[31]  F. Rossi,et al.  Identification of cofilin 1 as a candidate protein associated to mouse visual cortex plasticity , 2020, Neuroscience Letters.

[32]  E. Marcello,et al.  Dendritic Spines in Alzheimer’s Disease: How the Actin Cytoskeleton Contributes to Synaptic Failure , 2020, International journal of molecular sciences.

[33]  A. Borreca,et al.  Passive immunotherapy for N-truncated tau ameliorates the cognitive deficits in two mouse Alzheimer’s disease models , 2020, Brain communications.

[34]  M. Castelo‐Branco,et al.  Is the Retina a Mirror of the Aging Brain? Aging of Neural Retina Layers and Primary Visual Cortex Across the Lifespan , 2020, Frontiers in Aging Neuroscience.

[35]  Hans Op de Beeck,et al.  The Visual Acuity of Rats in Touchscreen Setups , 2019, Vision.

[36]  R. Rissman,et al.  Reflections on the Utility of the Retina as a Biomarker for Alzheimer’s Disease: A Literature Review , 2019, Neurology and Therapy.

[37]  D. Kang,et al.  Cofilin, a Master Node Regulating Cytoskeletal Pathogenesis in Alzheimer’s Disease , 2019, Journal of Alzheimer's disease : JAD.

[38]  S. Middei,et al.  Activity-Induced Amyloid-β Oligomers Drive Compensatory Synaptic Rearrangements in Brain Circuits Controlling Memory of Presymptomatic Alzheimer's Disease Mice , 2019, Biological Psychiatry.

[39]  A. Mauleon,et al.  Visual impairment in aging and cognitive decline: experience in a Memory Clinic , 2019, Scientific Reports.

[40]  Keith A. Johnson,et al.  Visual cognition in non-amnestic Alzheimer's disease: Relations to tau, amyloid, and cortical atrophy , 2019, NeuroImage: Clinical.

[41]  O. Garaschuk,et al.  Role of intracellular Ca2+ stores for an impairment of visual processing in a mouse model of Alzheimer's disease , 2019, Neurobiology of Disease.

[42]  Tim Cootes,et al.  Measuring vision using innate behaviours in mice with intact and impaired retina function , 2019, bioRxiv.

[43]  M. Castelo‐Branco,et al.  The Retina as a Window or Mirror of the Brain Changes Detected in Alzheimer’s Disease: Critical Aspects to Unravel , 2019, Molecular Neurobiology.

[44]  C. Murphy Olfactory and other sensory impairments in Alzheimer disease , 2018, Nature Reviews Neurology.

[45]  P. Scheltens,et al.  Amyloid-beta and phosphorylated tau in post-mortem Alzheimer’s disease retinas , 2018, Acta neuropathologica communications.

[46]  A. Buisson,et al.  Synaptotoxicity in Alzheimer's Disease Involved a Dysregulation of Actin Cytoskeleton Dynamics through Cofilin 1 Phosphorylation , 2018, The Journal of Neuroscience.

[47]  R. González-Reyes,et al.  Visual Features in Alzheimer's Disease: From Basic Mechanisms to Clinical Overview , 2018, Neural plasticity.

[48]  Antonino Cattaneo,et al.  The retina as a window to early dysfunctions of Alzheimer's disease following studies with a 5xFAD mouse model , 2018, Neurobiology of Aging.

[49]  L. Arckens,et al.  Anatomical correlates of rapid eye movement sleep-dependent plasticity in the developing cortex , 2018, Sleep.

[50]  M. Sur,et al.  Locally coordinated synaptic plasticity of visual cortex neurons in vivo , 2018, Science.

[51]  O. Rawashdeh,et al.  Early postnatal development of the visual cortex in mice with retinal degeneration , 2018, Mechanisms of Development.

[52]  Shawn R. Olsen,et al.  First spikes in visual cortex enable perceptual discrimination , 2018, bioRxiv.

[53]  D. Bennett,et al.  Aβ mediates F-actin disassembly in dendritic spines leading to cognitive deficits in Alzheimer's disease , 2017, The Journal of Neuroscience.

[54]  C. Bramham,et al.  Arc protein: a flexible hub for synaptic plasticity and cognition. , 2017, Seminars in cell & developmental biology.

[55]  Benjamin J Clark,et al.  Behavioral and Neural Subsystems of Rodent Exploration. , 2017, Learning and motivation.

[56]  G. Peyman,et al.  Visual system manifestations of Alzheimer's disease , 2017, Acta ophthalmologica.

[57]  M. Votruba,et al.  Can the retina be used to diagnose and plot the progression of Alzheimer's disease? , 2017, Acta ophthalmologica.

[58]  T. Burne,et al.  Touchscreen-based Visual Discrimination and Reversal Tasks for Mice to Test Cognitive Flexibility. , 2017, Bio-protocol.

[59]  T. Steckler,et al.  Evaluating aged mice in three touchscreen tests that differ in visual demands: Impaired cognitive function and impaired visual abilities , 2017, Behavioural Brain Research.

[60]  C. Louis,et al.  Tau accumulation in the retina promotes early neuronal dysfunction and precedes brain pathology in a mouse model of Alzheimer’s disease , 2017, Molecular Neurodegeneration.

[61]  B. Winblad,et al.  APP mouse models for Alzheimer's disease preclinical studies , 2017, The EMBO journal.

[62]  Sonja B. Hofer,et al.  Synaptic organization of visual space in primary visual cortex , 2017, Nature.

[63]  M. Bear,et al.  Arc restores juvenile plasticity in adult mouse visual cortex , 2017, Proceedings of the National Academy of Sciences.

[64]  R. Martins,et al.  Beta-amyloid sequelae in the eye: a critical review on its diagnostic significance and clinical relevance in Alzheimer’s disease , 2017, Molecular Psychiatry.

[65]  M. Stryker,et al.  Locomotion Induces Stimulus-Specific Response Enhancement in Adult Visual Cortex , 2017, The Journal of Neuroscience.

[66]  K. Black,et al.  Ocular indicators of Alzheimer’s: exploring disease in the retina , 2016, Acta Neuropathologica.

[67]  J. Bamburg,et al.  Actin dynamics and cofilin‐actin rods in alzheimer disease , 2016, Cytoskeleton.

[68]  M. Castelo‐Branco,et al.  Three-Dimensional Face Recognition in Mild Cognitive Impairment: A Psychophysical and Structural MR Study , 2016, Journal of the International Neuropsychological Society.

[69]  J. Cunha,et al.  Alzheimer’s disease: A review of its visual system neuropathology. Optical coherence tomography—a potential role as a study tool in vivo , 2016, Graefe's Archive for Clinical and Experimental Ophthalmology.

[70]  M. Cordeiro,et al.  Visual and Ocular Manifestations of Alzheimer’s Disease and Their Use as Biomarkers for Diagnosis and Progression , 2016, Front. Neurol..

[71]  Tobias Bonhoeffer,et al.  Selective Persistence of Sensorimotor Mismatch Signals in Visual Cortex of Behaving Alzheimer’s Disease Mice , 2016, Current Biology.

[72]  Mriganka Sur,et al.  Distinct roles of visual, parietal, and frontal motor cortices in memory-guided sensorimotor decisions , 2016, eLife.

[73]  Erin L. Abner,et al.  A Comprehensive Behavioral Test Battery to Assess Learning and Memory in 129S6/Tg2576 Mice , 2016, PloS one.

[74]  F. Bermúdez-Rattoni,et al.  Spatial Memory Impairment is Associated with Intraneural Amyloid-β Immunoreactivity and Dysfunctional Arc Expression in the Hippocampal-CA3 Region of a Transgenic Mouse Model of Alzheimer's Disease. , 2016, Journal of Alzheimer's disease : JAD.

[75]  Zhen Yan,et al.  Partial Amelioration of Synaptic and Cognitive Deficits by Inhibiting Cofilin Dephosphorylation in an Animal Model of Alzheimer's Disease. , 2016, Journal of Alzheimer's disease : JAD.

[76]  Daoyun Ji,et al.  Activities of visual cortical and hippocampal neurons co-fluctuate in freely moving rats during spatial behavior , 2015, eLife.

[77]  Richard Armstrong,et al.  Oculo‐visual changes and clinical considerations affecting older patients with dementia , 2015, Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians.

[78]  Georg B. Keller,et al.  Learning Enhances Sensory and Multiple Non-sensory Representations in Primary Visual Cortex , 2015, Neuron.

[79]  A. Borreca,et al.  CREB Regulates Experience-Dependent Spine Formation and Enlargement in Mouse Barrel Cortex , 2015, Neural plasticity.

[80]  Urmi Sengupta,et al.  Tau Immunotherapy Modulates Both Pathological Tau and Upstream Amyloid Pathology in an Alzheimer's Disease Mouse Model , 2015, The Journal of Neuroscience.

[81]  E. Weeber,et al.  RanBP9 at the intersection between cofilin and Aβ pathologies: rescue of neurodegenerative changes by RanBP9 reduction , 2015, Cell Death and Disease.

[82]  E. Weeber,et al.  Slingshot-Cofilin activation mediates mitochondrial and synaptic dysfunction via Aβ ligation to β1-integrin conformers , 2015, Cell Death and Differentiation.

[83]  Donald A. Wilson,et al.  At the interface of sensory and motor dysfunctions and Alzheimer's disease , 2015, Alzheimer's & Dementia.

[84]  I. Milenkovic,et al.  Patterns of Tau and α-Synuclein Pathology in the Visual System. , 2015, Journal of Parkinson's disease.

[85]  Sébastien Mosser,et al.  Inactivation of brain Cofilin-1 by age, Alzheimer's disease and γ-secretase. , 2014, Biochimica et biophysica acta.

[86]  Nicholas J. Priebe,et al.  Mouse vision as a gateway for understanding how experience shapes neural circuits , 2014, Front. Neural Circuits.

[87]  C. Eroglu,et al.  Rapid Golgi Analysis Method for Efficient and Unbiased Classification of Dendritic Spines , 2014, PloS one.

[88]  Richard M. Lipkin,et al.  Reliable and durable Golgi staining of brain tissue from human autopsies and experimental animals , 2014, Journal of Neuroscience Methods.

[89]  B. Hyman,et al.  Tau pathology does not affect experience-driven single-neuron and network-wide Arc/Arg3.1 responses , 2014, Acta neuropathologica communications.

[90]  Adrian G. Palacios,et al.  Alzheimer's disease in the human eye. Clinical tests that identify ocular and visual information processing deficit as biomarkers , 2014, Alzheimer's & Dementia.

[91]  P. Dodd,et al.  Cofilin rods and aggregates concur with tau pathology and the development of Alzheimer's disease. , 2014, Journal of Alzheimer's disease : JAD.

[92]  M. Belkin,et al.  Correlation between visual acuity and cognitive functions , 2013, British Journal of Ophthalmology.

[93]  Miguel Castelo-Branco,et al.  Impaired processing of 3D motion-defined faces in mild cognitive impairment and healthy aging: an fMRI study. , 2013, Cerebral cortex.

[94]  Bradley T. Hyman,et al.  Human LilrB2 Is a β-Amyloid Receptor and Its Murine Homolog PirB Regulates Synaptic Plasticity in an Alzheimer’s Model , 2013, Science.

[95]  K. Steece-Collier,et al.  Advances in thin tissue Golgi-Cox impregnation: Fast, reliable methods for multi-assay analyses in rodent and non-human primate brain , 2013, Journal of Neuroscience Methods.

[96]  C. Mathis,et al.  Detecting spatial memory deficits beyond blindness in tg2576 Alzheimer mice , 2013, Neurobiology of Aging.

[97]  James E. Morgan,et al.  Retinal ganglion cell dendritic degeneration in a mouse model of Alzheimer's disease , 2012, Neurobiology of Aging.

[98]  M. Schwartz,et al.  The retina as a window to the brain—from eye research to CNS disorders , 2013, Nature Reviews Neurology.

[99]  R. Chang,et al.  Review: Tauopathy in the retina and optic nerve: does it shadow pathological changes in the brain? , 2012, Molecular vision.

[100]  G. Paxinos,et al.  Paxinos and Franklin's the Mouse Brain in Stereotaxic Coordinates , 2012 .

[101]  M. Eguchi,et al.  Orchestrated experience-driven Arc/Arg3.1 responses are disrupted in a mouse model of Alzheimer’s disease , 2012, Nature Neuroscience.

[102]  K. Stover,et al.  Age-related changes in visual acuity, learning and memory in the APPswe/PS1dE9 mouse model of Alzheimer's disease , 2012, Behavioural Brain Research.

[103]  Elly Nedivi,et al.  Clustered Dynamics of Inhibitory Synapses and Dendritic Spines in the Adult Neocortex , 2012, Neuron.

[104]  A. Atlante,et al.  Interaction between NH2-tau fragment and Aβ in Alzheimer's disease mitochondria contributes to the synaptic deterioration , 2012, Neurobiology of Aging.

[105]  D. Kang,et al.  Pivotal role of the RanBP9-cofilin pathway in Aβ-induced apoptosis and neurodegeneration , 2012, Cell Death and Differentiation.

[106]  Daniel N. Hill,et al.  Staged decline of neuronal function in vivo in an animal model of Alzheimer's disease , 2012, Nature Communications.

[107]  R. Maccioni,et al.  Fibrillar amyloid-β1-42 modifies actin organization affecting the cofilin phosphorylation state: a role for Rac1/cdc42 effector proteins and the slingshot phosphatase. , 2012, Journal of Alzheimer's disease : JAD.

[108]  Hongbo Yu,et al.  Rapid experience-dependent plasticity of synapse function and structure in ferret visual cortex in vivo , 2011, Proceedings of the National Academy of Sciences.

[109]  Kathrin Finke,et al.  Staged decline of visual processing capacity in mild cognitive impairment and Alzheimer's disease , 2011, Neurobiology of Aging.

[110]  B. Hyman,et al.  Soluble tau Species, Not Neurofibrillary Aggregates, Disrupt Neural System Integration in a tau Transgenic Model , 2011, Journal of neuropathology and experimental neurology.

[111]  A. Smit,et al.  The Synaptic Proteome during Development and Plasticity of the Mouse Visual Cortex* , 2011, Molecular & Cellular Proteomics.

[112]  A. Bacci,et al.  Caspase-3 triggers early synaptic dysfunction in a mouse model of Alzheimer's disease , 2011, Nature Neuroscience.

[113]  D. Selkoe,et al.  Amyloid beta dimers/trimers potently induce cofilin-actin rods that are inhibited by maintaining cofilin-phosphorylation , 2011, Molecular Neurodegeneration.

[114]  Mriganka Sur,et al.  Structural Dynamics of Synapses in Vivo Correlate with Functional Changes during Experience-Dependent Plasticity in Visual Cortex , 2010, The Journal of Neuroscience.

[115]  P. Worley,et al.  A Specific Requirement of Arc/Arg3.1 for Visual Experience-Induced Homeostatic Synaptic Plasticity in Mouse Primary Visual Cortex , 2010, The Journal of Neuroscience.

[116]  Stephan Bandelow,et al.  Visual impairment in Alzheimer's disease: a critical review. , 2010, Journal of Alzheimer's disease : JAD.

[117]  T. O'Leary,et al.  Visuo-spatial learning and memory deficits on the Barnes maze in the 16-month-old APPswe/PS1dE9 mouse model of Alzheimer's disease , 2009, Behavioural Brain Research.

[118]  F. LaFerla,et al.  Relevance of Transgenic Mouse Models to Human Alzheimer Disease* , 2009, Journal of Biological Chemistry.

[119]  W. M. Keck,et al.  Highly Selective Receptive Fields in Mouse Visual Cortex , 2008, The Journal of Neuroscience.

[120]  M. Ciotti,et al.  Identification of a caspase-derived N-terminal tau fragment in cellular and animal Alzheimer's disease models , 2008, Molecular and Cellular Neuroscience.

[121]  B. Alescio-Lautier,et al.  Visual and visuospatial short-term memory in mild cognitive impairment and Alzheimer disease: Role of attention , 2007, Neuropsychologia.

[122]  M. Maloney,et al.  Cofilin-mediated neurodegeneration in alzheimer’s disease and other amyloidopathies , 2007, Molecular Neurobiology.

[123]  Kara L. Agster,et al.  Functional neuroanatomy of the parahippocampal region in the rat: The perirhinal and postrhinal cortices , 2007, Hippocampus.

[124]  L. Mucke,et al.  Reducing Endogenous Tau Ameliorates Amyloid ß-Induced Deficits in an Alzheimer's Disease Mouse Model , 2007, Science.

[125]  Fatmire Berisha,et al.  Retinal abnormalities in early Alzheimer's disease. , 2007, Investigative ophthalmology & visual science.

[126]  L. Maffei,et al.  Transient Synaptic Silencing of Developing Striate Cortex Has Persistent Effects on Visual Function and Plasticity , 2007, The Journal of Neuroscience.

[127]  R. Schliebs,et al.  Increase of locomotor activity underlying the behavioral disinhibition in tg2576 mice. , 2007, Behavioral neuroscience.

[128]  Richard E Brown,et al.  The influence of visual ability on learning and memory performance in 13 strains of mice. , 2007, Learning & memory.

[129]  Mike Anderson,et al.  Inspection time in non-demented older adults with mild cognitive impairment , 2006, Neuropsychologia.

[130]  Susumu Tonegawa,et al.  In Vivo Two-Photon Imaging Reveals a Role of Arc in Enhancing Orientation Specificity in Visual Cortex , 2006, Cell.

[131]  R. E. Brown,et al.  Visual detection, pattern discrimination and visual acuity in 14 strains of mice , 2006, Genes, brain, and behavior.

[132]  Karel Svoboda,et al.  Experience-dependent and cell-type-specific spine growth in the neocortex , 2006, Nature.

[133]  Sudha Seshadri,et al.  Visual Association Pathology in Preclinical Alzheimer Disease , 2006, Journal of neuropathology and experimental neurology.

[134]  Mark Bowlby,et al.  Early-onset behavioral and synaptic deficits in a mouse model of Alzheimer's disease. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[135]  G. Gilmore,et al.  Enhanced stimulus contrast normalizes visual processing of rapidly presented letters in Alzheimer’s disease , 2005, Vision Research.

[136]  D. Bennett,et al.  Reduction of choline acetyltransferase activity in primary visual cortex in mild to moderate Alzheimer's disease. , 2005, Archives of neurology.

[137]  Andrea Tales,et al.  Abnormal visual search in mild cognitive impairment and Alzheimer’s disease , 2005, Neurocase.

[138]  Patrick O Kanold,et al.  Multiple periods of functional ocular dominance plasticity in mouse visual cortex , 2005, Nature Neuroscience.

[139]  Carol A Barnes,et al.  Spatial Exploration-Induced Arc mRNA and Protein Expression: Evidence for Selective, Network-Specific Reactivation , 2005, The Journal of Neuroscience.

[140]  K. Schilling,et al.  Characterization of the neuronal marker NeuN as a multiply phosphorylated antigen with discrete subcellular localization , 2005, Journal of neuroscience research.

[141]  G. Laviola,et al.  Aspects of spatial memory and behavioral disinhibition in Tg2576 transgenic mice as a model of Alzheimer’s disease , 2005, Behavioural Brain Research.

[142]  Mark F Bear,et al.  A Morphological Correlate of Synaptic Scaling in Visual Cortex , 2022 .

[143]  G. Riedel,et al.  Visual acuity in the water maze: sensitivity to muscarinic receptor blockade in rats and mice , 2004, Behavioural Brain Research.

[144]  J. Guzowski,et al.  Amyloid suppresses induction of genes critical for memory consolidation in APP + PS1 transgenic mice , 2003, Journal of neurochemistry.

[145]  M. Farah,et al.  Visual object and face processing in mild-to-moderate Alzheimer’s disease: from segmentation to imagination , 2003, Neuropsychologia.

[146]  T. Lanz,et al.  Dendritic spine loss in the hippocampus of young PDAPP and Tg2576 mice and its prevention by the ApoE2 genotype , 2003, Neurobiology of Disease.

[147]  Robert Lalonde,et al.  Transgenic mice expressing the βAPP 695SWE mutation: effects on exploratory activity, anxiety, and motor coordination , 2003, Brain Research.

[148]  John R Hodges,et al.  Dissociation between top‐down attentional control and the time course of visual attention as measured by attentional dwell time in patients with mild cognitive impairment , 2003, The European journal of neuroscience.

[149]  J. Loring,et al.  Selectively Reduced Expression of Synaptic Plasticity-Related Genes in Amyloid Precursor Protein + Presenilin-1 Transgenic Mice , 2003, The Journal of Neuroscience.

[150]  Charles J Duffy,et al.  Attentional dynamics and visual perception: mechanisms of spatial disorientation in Alzheimer's disease. , 2003, Brain : a journal of neurology.

[151]  Xudong Huang,et al.  Cytosolic β-amyloid deposition and supranuclear cataracts in lenses from people with Alzheimer's disease , 2003, The Lancet.

[152]  Frank Tong,et al.  Cognitive neuroscience: Primary visual cortex and visual awareness , 2003, Nature Reviews Neuroscience.

[153]  C. Masters,et al.  Cytosolic beta-amyloid deposition and supranuclear cataracts in lenses from people with Alzheimer's disease. , 2003, Lancet.

[154]  C. Cotman,et al.  Caspase-9 Activation and Caspase Cleavage of tau in the Alzheimer's Disease Brain , 2002, Neurobiology of Disease.

[155]  M. Grossman,et al.  Visual perceptual functions predict instrumental activities of daily living in patients with dementia. , 2002, Neuropsychiatry, neuropsychology, and behavioral neurology.

[156]  L. Maffei,et al.  Requirement of ERK Activation for Visual Cortical Plasticity , 2001, Science.

[157]  H. Bridge,et al.  Visual discrimination learning in the water maze: a novel test for visual acuity , 2001, Behavioural Brain Research.

[158]  M. Tovée,et al.  Contrast sensitivity and visual acuity in patients with Alzheimer's disease , 2000, International journal of geriatric psychiatry.

[159]  R. Douglas,et al.  Behavioral assessment of visual acuity in mice and rats , 2000, Vision Research.

[160]  Mark Nawrot,et al.  Vision and cognition in Alzheimer’s disease , 2000, Neuropsychologia.

[161]  D. Amaral,et al.  Hippocampal‐neocortical interaction: A hierarchy of associativity , 2000, Hippocampus.

[162]  Bryan Kolb,et al.  A method for vibratome sectioning of Golgi–Cox stained whole rat brain , 1998, Journal of Neuroscience Methods.

[163]  S. Cappa,et al.  Visual and spatial perception in the early phase of Alzheimer's disease. , 1998, Neuropsychology.

[164]  George Paxinos,et al.  The Mouse Brain in Stereotaxic Coordinates , 2001 .

[165]  H. Braak,et al.  Staging of Alzheimer-related cortical destruction. , 1997, International psychogeriatrics.

[166]  R A Armstrong,et al.  Visual Field Defects in Alzheimer’s Disease Patients May Reflect Differential Pathology in the Primary Visual Cortex , 1996, Optometry and vision science : official publication of the American Academy of Optometry.

[167]  S. Younkin,et al.  Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice , 1996, Science.

[168]  R. Blanks,et al.  Retinal pathology in Alzheimer's disease. II. Regional neuron loss and glial changes in GCL , 1996, Neurobiology of Aging.

[169]  H. Kolb,et al.  The Primary Visual Cortex -- Webvision: The Organization of the Retina and Visual System , 1995 .

[170]  G. Leuba,et al.  Visual cortex in Alzheimer's disease: Occurencee of neuronal death and glial proliferation, and correlation with pathological hallmarks , 1994, Neurobiology of Aging.

[171]  M. Glickstein,et al.  Afferent and Efferent Connections of Temporal Association Cortex in the Rat: A Horseradish Peroxidase Study , 1991, The European journal of neuroscience.

[172]  J. Morrison,et al.  Quantitative analysis of a vulnerable subset of pyramidal neurons in Alzheimer's disease: II. Primary and secondary visual cortex , 1990, The Journal of comparative neurology.

[173]  H. Schägger,et al.  Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis for the separation of proteins in the range from 1 to 100 kDa. , 1987, Analytical biochemistry.

[174]  M J Campbell,et al.  Laminar and regional distributions of neurofibrillary tangles and neuritic plaques in Alzheimer's disease: a quantitative study of visual and auditory cortices , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[175]  G. Paxinos The Rat nervous system , 1985 .

[176]  B. Vogt,et al.  Direct connections of rat visual cortex with sensory, motor, and association cortices , 1984, The Journal of comparative neurology.

[177]  M. Moscovitch,et al.  Visual processing deficits as assessed by spatial frequency contrast sensitivity and backward masking in normal ageing and Alzheimer's disease. , 1984, Brain : a journal of neurology.