Distribution of amyloid beta 42 in relation to the cerebral microvasculature in an elderly cohort with Alzheimer's disease.
Amyloid beta (A beta) deposits and neurofibrillary pathology are characteristic features of Alzheimer's disease (AD). The association of A beta with cerebral vessels is an intriguing feature of AD. While some degree of cerebral A beta angiopathy involving the leptomeninges and intraparenchymal vessels occurs in almost all cases of AD, the proportion of microvessels within a neocortical region containing deposits of A beta peptide is not known. In this study, we examined a cohort of clinically and pathologically evaluated AD cases to assess the percentage of cerebral microvessels in the temporal cortex and parahippocampal gyrus associated with the predominant, A beta 42 form of the peptide. We also assessed whether the distribution and burden of amyloid was related to apolipoprotein E (APOE) genotype. Using double immunostaining methods, we surprisingly found that at least 40% of the microvessels in the two brain regions contained A beta 42 deposits. There was no correlation of such localization with APOE genotype, however, epsilon 4 homozygotes revealed a greater burden of A beta 40. These observations suggest that high proportions of cortical microvessels are associated with A beta 42, which may affect microvascular function.
Thomas
A J
AJ
Wolfson Research Centre, Newcastle General Hospital, Newcastle upon Tyne, United Kingdom. a.j.thomas@ncl.ac.uk
Morris
C M
CM
Ferrier
I N
IN
Kalaria
R N
RN
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000032:analysis*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D002560:Cerebrovascular Circulation; D015331:Cohort Studies; D018891:Dentate Gyrus / Q000098:blood supply / Q000473:pathology; D005260:Female; D006624:Hippocampus / Q000098:blood supply* / Q000473:pathology*; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000473:pathology*; D010446:Peptide Fragments / Q000032:analysis*; D013702:Temporal Lobe / Q000098:blood supply* / Q000473:pathology*
D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)