Relationship of neurofibrillary pathology to cerebral amyloid angiopathy in Alzheimer's disease.
Over 90% of patients with Alzheimer's disease (AD) develop cerebral amyloid angiopathy (CAA). Severe dyshoric CAA, in which amyloid extends into the surrounding brain parenchyma, may be associated with adjacent clustering of tau-immunopositive neurites but the relationship of CAA to neurofibrillary pathology has not been systematically investigated. In the present study this relationship was examined in sections of frontal, temporal and parietal cortex from 25 AD patients with moderate to severe CAA and 26 with mild or absent CAA. We measured immunolabelling of abnormally phosphorylated tau adjacent to A beta-laden and non-A beta-laden arteries and arterioles, and in cortex away from arteries and arterioles. We also analysed the possible influence of APOE genotype on these measurements. There were no significant differences between the lobes in measurements of tau labelling, either around blood vessels or elsewhere in the cortex. However, tau labelling around A beta-laden arteries and arterioles significantly exceeded that around non-A beta-laden blood vessels (P<0.001) and this, in turn was greater than the labelling of cortex away from blood vessels (P<0.001). There was no association between APOE epsilon 4 and the immunolabelling density for tau, whether around amyloid- or non-amyloid-laden arteries and arterioles, or in the cerebral cortex away from these. We propose that both CAA and peri-vascular accumulation of hyperphosphorylated tau may be a consequence of elevated levels of soluble A beta around cortical arteries and arterioles.
Williams
S
S
Care of the Elderly, Institute of Clinical Neurosciences, Department of Clinical Science at North Bristol, University of Bristol, Bristol, UK.
Chalmers
K
K
Wilcock
G K
GK
Love
S
S
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics; D001158:Arteries / Q000378:metabolism / Q000473:pathology; D001160:Arterioles / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000098:blood supply / Q000473:pathology*; D016657:Cerebral Amyloid Angiopathy / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D016875:tau Proteins / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D016875:tau Proteins