Alzheimer's disease

Alzheimer's disease, the commonest cause of dementia, is a growing global health concern with huge implications for individuals and society. In this review, current understanding of the epidemiology, genetics, pathology and pathogenesis of Alzheimer's disease is outlined, before its clinical presentation and current treatment strategies are discussed. Finally, the review discusses how our enhanced understanding of Alzheimer pathogenesis, including the recognition of a protracted preclinical phase, is informing new therapeutic strategies with the aim of moving from treatment to prevention.

[1]  D. Selkoe,et al.  Soluble amyloid β-protein dimers isolated from Alzheimer cortex directly induce Tau hyperphosphorylation and neuritic degeneration , 2011, Proceedings of the National Academy of Sciences.

[2]  G. Forloni,et al.  Oligomeropathies and pathogenesis of Alzheimer and Parkinson's diseases , 2016, Movement disorders : official journal of the Movement Disorder Society.

[3]  Mathias Jucker,et al.  Self-propagation of pathogenic protein aggregates in neurodegenerative diseases , 2013, Nature.

[4]  B. Hyman,et al.  Neuropathological alterations in Alzheimer disease. , 2011, Cold Spring Harbor perspectives in medicine.

[5]  R. Coleman,et al.  Use of florbetapir-PET for imaging beta-amyloid pathology. , 2011, JAMA.

[6]  K. Blennow,et al.  CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis , 2016, The Lancet Neurology.

[7]  K. Davis.  Cholinesterase Inhibitors in Alzheimer's Disease , 1994, Neuropsychopharmacology.

[8]  Sandra E Black,et al.  Clinical, imaging, and pathological heterogeneity of the Alzheimer's disease syndrome , 2013, Alzheimer's Research & Therapy.

[9]  John Seibyl,et al.  Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer's disease: Phase 3 study , 2015, Alzheimer's & Dementia.

[10]  H. Braak,et al.  Neuropathological stageing of Alzheimer-related changes , 2004, Acta Neuropathologica.

[11]  J. Schneider,et al.  National Institute on Aging–Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease , 2012, Alzheimer's & Dementia.

[12]  C. Rowe,et al.  Aβ-amyloid and Tau Imaging in Dementia. , 2017, Seminars in nuclear medicine.

[13]  A. Alzheimer.  Uber eine eigenartige Erkrankung der Hirnrinde , 1907 .

[14]  C. Jack,et al.  Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade , 2010, The Lancet Neurology.

[15]  P. Lantos,et al.  Pathology of familial Alzheimer's disease with Lewy bodies. , 1997, Journal of neural transmission. Supplementum.

[16]  Eric Karran,et al.  The Cellular Phase of Alzheimer’s Disease , 2016, Cell.

[17]  J. Hardy,et al.  The Amyloid Hypothesis of Alzheimer ’ s Disease : Progress and Problems on the Road to Therapeutics , 2009 .

[18]  Paul Edison,et al.  Does Microglial Activation Influence Hippocampal Volume and Neuronal Function in Alzheimer's Disease and Parkinson's Disease Dementia? , 2016, Journal of Alzheimer's disease : JAD.

[19]  Nick C Fox,et al.  Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria , 2014, The Lancet Neurology.

[20]  Denise C. Park,et al.  Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease , 2011, Alzheimer's & Dementia.

[21]  J. Karlawish,et al.  The A4 Study: Stopping AD Before Symptoms Begin? , 2014, Science Translational Medicine.

[22]  A. Spector,et al.  Psychological treatments for depression and anxiety in dementia and mild cognitive impairment: systematic review and meta-analysis† , 2015, British Journal of Psychiatry.

[23]  M. Gill,et al.  Common polygenic variation enhances risk prediction for Alzheimer's disease. , 2015, Brain : a journal of neurology.

[24]  M N Rossor,et al.  Preclinical trials in autosomal dominant AD: implementation of the DIAN-TU trial. , 2013, Revue neurologique.

[25]  Chengjie Xiong,et al.  Autosomal-dominant Alzheimer's disease: a review and proposal for the prevention of Alzheimer's disease , 2011, Alzheimer's Research & Therapy.

[26]  Nick C Fox,et al.  The clinical use of structural MRI in Alzheimer disease , 2010, Nature Reviews Neurology.

[27]  J. Morris,et al.  The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease , 2011, Alzheimer's & Dementia.

[28]  A. Goate,et al.  Alzheimer’s Disease Risk Genes and Mechanisms of Disease Pathogenesis , 2015, Biological Psychiatry.

[29]  Olivier Colliot,et al.  Early and protective microglial activation in Alzheimer's disease: a prospective study using 18F-DPA-714 PET imaging. , 2016, Brain : a journal of neurology.

[30]  S. Pocock,et al.  BMI and risk of dementia in two million people over two decades: a retrospective cohort study. , 2015, The lancet. Diabetes & endocrinology.

[31]  N. Herrmann,et al.  Beyond immunotherapy: new approaches for disease modifying treatments for early Alzheimer’s disease , 2016, Expert opinion on pharmacotherapy.

[32]  Robert Barber,et al.  Nursing home placement in the Donepezil and Memantine in Moderate to Severe Alzheimer's Disease (DOMINO-AD) trial: secondary and post-hoc analyses , 2015, The Lancet Neurology.

[33]  Paul Edison,et al.  Neuroinflammation in Alzheimer's disease: Current evidence and future directions , 2016, Alzheimer's & Dementia.

[34]  K. Rhodes,et al.  The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease , 2016, Nature.

[35]  C. Lyketsos,et al.  Assessment and management of behavioral and psychological symptoms of dementia , 2015, BMJ : British Medical Journal.

[36]  C. Ballard,et al.  Neuroleptic drugs in dementia: benefits and harm , 2006, Nature Reviews Neuroscience.

[37]  The Lancet Neurology.  Antipsychotic drugs for dementia: a balancing act , 2009, The Lancet Neurology.

[38]  J. Ashford,et al.  Comparison of Neuropathologic Criteria for the Diagnosis of Alzheimer’s Disease , 1997, Neurobiology of Aging.

[39]  S. Mead,et al.  Review: An update on clinical, genetic and pathological aspects of frontotemporal lobar degenerations , 2015, Neuropathology and applied neurobiology.

[40]  J. Harrison,et al.  Posterior cortical atrophy. , 1989, Clinical and experimental neurology.

[41]  Nick C Fox,et al.  Clinical and biomarker changes in dominantly inherited Alzheimer's disease. , 2012, The New England journal of medicine.

[42]  A. Heyman,et al.  The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) , 1993, Neurology.

[43]  Ole A. Andreassen,et al.  A mutation in APP protects against Alzheimer’s disease and age-related cognitive decline , 2012, Nature.

[44]  Akinori Nakamura,et al.  Brain fluorodeoxyglucose (FDG) PET in dementia , 2016, Ageing Research Reviews.

[45]  D. Holtzman,et al.  Apolipoprotein E in Alzheimer's disease and other neurological disorders , 2011, The Lancet Neurology.

[46]  J. Trojanowski,et al.  Editorial on Consensus Recommendations for the Postmortem Diagnosis of Alzheimer Disease from the National Institute on Aging and the Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Assessment of Alzheimer Disease , 1997, Journal of neuropathology and experimental neurology.

[47]  Kewei Chen,et al.  Alzheimer's Prevention Initiative: a plan to accelerate the evaluation of presymptomatic treatments. , 2011, Journal of Alzheimer's disease : JAD.

[48]  M. Albert,et al.  Early Aβ accumulation and progressive synaptic loss, gliosis, and tangle formation in AD brain , 2004, Neurology.

[49]  M. Rossor,et al.  Correlating familial Alzheimer's disease gene mutations with clinical phenotype. , 2010, Biomarkers in medicine.

[50]  S. Leurgans,et al.  The neuropathology of probable Alzheimer disease and mild cognitive impairment , 2009, Annals of neurology.

[51]  Teng Jiang,et al.  Meta-analysis of modifiable risk factors for Alzheimer's disease , 2015, Journal of Neurology, Neurosurgery & Psychiatry.

[52]  J. Hardy,et al.  A Critique of the Drug Discovery and Phase 3 Clinical Programs Targeting the Amyloid Hypothesis for Alzheimer Disease , 2014, Annals of neurology.

[53]  Nick C Fox,et al.  Common variants in ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer’s disease , 2011, Nature Genetics.

[54]  Nick C Fox,et al.  Study protocol: Insight 46 – a neuroscience sub-study of the MRC National Survey of Health and Development , 2017, BMC Neurology.

[55]  Y. Yakushiji.  Cerebral Microbleeds: Detection, Associations and Clinical Implications. , 2015, Frontiers of neurology and neuroscience.

[56]  J. Hardy,et al.  The amyloid hypothesis of Alzheimer's disease at 25 years , 2016, EMBO molecular medicine.

[57]  D. Bennett,et al.  TDP-43 stage, mixed pathologies, and clinical Alzheimer's-type dementia. , 2016, Brain : a journal of neurology.

[58]  C. Jack,et al.  Preclinical Alzheimer's disease: Definition, natural history, and diagnostic criteria , 2016, Alzheimer's & Dementia.

[59]  V. Henderson.  Alzheimer's disease and other neurological disorders , 2007, Climacteric : the journal of the International Menopause Society.

[60]  Seth Love,et al.  Genetic Evidence Implicates the Immune System and Cholesterol Metabolism in the Aetiology of Alzheimer's Disease , 2010, PloS one.

[61]  Martin Prince,et al.  World Alzheimer Report 2014: Dementia and risk reduction: An analysis of protective and modifiable risk factors , 2014 .

[62]  Antonio Lobo,et al.  Dementia in western Europe: epidemiological evidence and implications for policy making , 2016, The Lancet Neurology.

[63]  H. Braak,et al.  Phases of Aβ-deposition in the human brain and its relevance for the development of AD , 2002, Neurology.

[64]  J. Schott,et al.  Blood Biomarkers for Alzheimer’s Disease: Much Promise, Cautious Progress , 2016, Molecular Diagnosis & Therapy.

[65]  Nick C Fox,et al.  The Diagnosis of Mild Cognitive Impairment due to Alzheimer’s Disease: Recommendations from the National Institute on Aging-Alzheimer’s Association Workgroups on Diagnostic Guidelines for Alzheimer’s Disease , 2011 .

[66]  J. Molinuevo,et al.  EFNS‐ENS/EAN Guideline on concomitant use of cholinesterase inhibitors and memantine in moderate to severe Alzheimer's disease , 2015, European journal of neurology.

[67]  J T O'Brien,et al.  EFNS guidelines for the diagnosis and management of Alzheimer’s disease , 2010, European journal of neurology.

[68]  G. Grossberg,et al.  The Natural History of Alzheimer's Disease: A Brain Bank Study , 1995, Journal of the American Geriatrics Society.

[69]  F. Sherriff,et al.  Memantine for dementia. , 2005, The Cochrane database of systematic reviews.

[70]  Charles D. Smith,et al.  “New Old Pathologies”: AD, PART, and Cerebral Age-Related TDP-43 With Sclerosis (CARTS) , 2016, Journal of neuropathology and experimental neurology.

[71]  T. Dening,et al.  Antidepressants for treating depression in dementia. , 2002, The Cochrane database of systematic reviews.

[72]  B. Miller,et al.  Classification of primary progressive aphasia and its variants , 2011, Neurology.

[73]  L. Robinson,et al.  A two decade dementia incidence comparison from the Cognitive Function and Ageing Studies I and II , 2016, Nature Communications.