Patterns of cerebral amyloid angiopathy define histopathological phenotypes in Alzheimer's disease

Pathological heterogeneity of Aβ deposition in senile plaques (SP) and cerebral amyloid angiopathy (CAA) in Alzheimer's disease (AD) has been long noted. The aim of this study was to classify cases of AD according to their pattern of Aβ deposition, and to seek factors which might predict, or predispose towards, this heterogeneity.

[1]  D. Mann,et al.  Negative association between amyloid plaques and cerebral amyloid angiopathy in Alzheimer's disease , 2003, Neuroscience Letters.

[2]  H. Soininen,et al.  Alzheimer pathology of patients carrying apoliprotein E ϵ4 allele , 1995, Neurobiology of Aging.

[3]  S. D. Preston,et al.  Capillary and arterial cerebral amyloid angiopathy in Alzheimer's disease: defining the perivascular route for the elimination of amyloid β from the human brain , 2003, Neuropathology and applied neurobiology.

[4]  Nick C Fox,et al.  Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease, and shows evidence for additional susceptibility genes , 2009, Nature Genetics.

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

[6]  D. Andreu,et al.  Lack of oestrogen protection in amyloid-mediated endothelial damage due to protein nitrotyrosination. , 2005, Brain : a journal of neurology.

[7]  C. Holmes,et al.  Neuropathology after active Aβ42 immunotherapy: implications for Alzheimer’s disease pathogenesis , 2010, Acta Neuropathologica.

[8]  J. Vonsattel,et al.  Cerebral amyloid angiopathy without and with cerebral hemorrhages: A comparative histological study , 1991, Annals of neurology.

[9]  B. Hyman,et al.  Apolipoprotein E epsilon 4 and cerebral hemorrhage associated with amyloid angiopathy. , 1995, Annals of neurology.

[10]  T. Iwatsubo,et al.  Visualization of Aβ42(43) and Aβ40 in senile plaques with end-specific Aβ monoclonals: Evidence that an initially deposited species is Aβ42(43) , 1994, Neuron.

[11]  J. Bading,et al.  Cerebrovascular Accumulation and Increased Blood‐Brain Barrier Permeability to Circulating Alzheimer's Amyloid β Peptide in Aged Squirrel Monkey with Cerebral Amyloid Angiopathy , 1998, Journal of neurochemistry.

[12]  Nick C Fox,et al.  Letter abstract - Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's Disease , 2009 .

[13]  D. Dickson,et al.  Extracellular Deposits of Aβ Produced in Cultures of Alzheimer Disease Brain Vascular Smooth Muscle Cells , 2005 .

[14]  C. Jack,et al.  Alzheimer's Disease Neuroimaging Initiative , 2008 .

[15]  D. Mann,et al.  Preferential deposition of amyloid β protein (Aβ) in the form Aβ 40 in Alzheimer's disease is associated with a gene dosage effect of the apolipoprotein E E4 allele , 1997, Neuroscience Letters.

[16]  B T Hyman,et al.  Senile dementia associated with amyloid beta protein angiopathy and tau perivascular pathology but not neuritic plaques in patients homozygous for the APOE-epsilon4 allele. , 2000, Acta neuropathologica.

[17]  Julie S. Snowden,et al.  Distinct Memory Profiles in Alzheimer's Disease , 2007, Cortex.

[18]  T. Iwatsubo,et al.  Visualization of A beta 42(43) and A beta 40 in senile plaques with end-specific A beta monoclonals: evidence that an initially deposited species is A beta 42(43). , 1994, Neuron.

[19]  O. J. Dunn.  Multiple Comparisons Using Rank Sums , 1964 .

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

[21]  J. Attems,et al.  Capillary cerebral amyloid angiopathy identifies a distinct APOE ε4-associated subtype of sporadic Alzheimer’s disease , 2010, Acta Neuropathologica.

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

[23]  K. Jellinger,et al.  Review: Sporadic cerebral amyloid angiopathy , 2011, Neuropathology and applied neurobiology.

[24]  H. Braak,et al.  Two Types of Sporadic Cerebral Amyloid Angiopathy , 2002, Journal of neuropathology and experimental neurology.

[25]  C. Behl.  Oestrogen as a neuroprotective hormone , 2002, Nature Reviews Neuroscience.

[26]  R N Kalaria,et al.  Apolipoprotein E-epsilon4 alleles in cerebral amyloid angiopathy and cerebrovascular pathology associated with Alzheimer's disease. , 1996, The American journal of pathology.

[27]  H. Soininen,et al.  Alzheimer pathology of patients carrying apolipoprotein E epsilon 4 allele. , 1995, Neurobiology of aging.

[28]  S. M. Sumi,et al.  The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) , 1991, Neurology.

[29]  Joseph B Hiatt,et al.  PI3K/AKT pathway mutations cause a spectrum of brain malformations from megalencephaly to focal cortical dysplasia. , 2015, Brain : a journal of neurology.

[30]  B. Hyman,et al.  Apolipoprotein E ϵ4 and cerebral hemorrhage associated with amyloid angiopathy , 1995 .

[31]  S. Love,et al.  APOEɛ4 influences the pathological phenotype of Alzheimer's disease by favouring cerebrovascular over parenchymal accumulation of Aβ protein , 2003 .

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

[33]  L. Thal,et al.  Cerebral infarction in Alzheimer's disease is associated with severe amyloid angiopathy and hypertension. , 1995, Archives of neurology.

[34]  Bradley T. Hyman,et al.  Senile dementia associated with amyloid β protein angiopathy and tau perivascular pathology but not neuritic plaques in patients homozygous for the APOE-ε4 allele , 2000, Acta Neuropathologica.

[35]  D. Graham,et al.  The Apolipoprotein E ∈2 Allele and the Pathological Features in Cerebral Amyloid Angiopathy-related Hemorrhage , 1999 .

[36]  D. Dickson,et al.  Extracellular deposits of A beta produced in cultures of Alzheimer disease brain vascular smooth muscle cells. , 2005, Journal of neuropathology and experimental neurology.

[37]  B. Hyman,et al.  Apolipoprotein E in sporadic Alzheimer's disease: Allelic variation and receptor interactions , 1993, Neuron.

[38]  Cornelia M van Duijn,et al.  Dense-core senile plaques in the Flemish variant of Alzheimer's disease are vasocentric. , 2002, The American journal of pathology.

[39]  P. Eikelenboom,et al.  Characteristics of Dyshoric Capillary Cerebral Amyloid Angiopathy , 2010, Journal of neuropathology and experimental neurology.

[40]  D. Mann,et al.  The prevalence of amyloid (A4) protein deposits within the cerebral and cerebellar cortex in Down's syndrome and Alzheimer's disease , 2004, Acta Neuropathologica.

[41]  K. Jellinger,et al.  Alzheimer’s disease pathology influences severity and topographical distribution of cerebral amyloid angiopathy , 2005, Acta Neuropathologica.

[42]  PhilipR. Wenham,et al.  Apolipoprotein E genotyping by one-stage PCR , 1991, The Lancet.