Diffuse plaques contain C-terminal A beta 42 and not A beta 40: evidence from cats and dogs.

Abstract:

:Recent reports have suggested that beta-amyloid (A beta) species of variable length C-termini are differentially deposited within early and late-stage plaques and the cerebrovasculature. Specifically, longer C-terminal length A beta 42/3 fragments (i.e., A beta forms extending to residues 42 and/or 43) are thought to be predominant within diffuse plaques while both A beta 42/3 and A beta 40 (A beta forms terminating at residue 40) are present within a subset of neuritic plaques and cerebrovascular deposits. We sought to clarify the issue of differential A beta deposition using aged canines, a partial animal model of Alzheimer's disease that exhibits extensive diffuse plaques and frequent vascular amyloid, but does not contain neuritic plaques or neurofibrillary tangles. We examined the brains of 20 aged canines, 3 aged felines, and 17 humans for the presence of A beta immunoreactive plaques, using antibodies to A beta 1(-17), A beta 17(-24), A beta 1(-28), A beta 40, and A beta 42. We report that plaques within the canine and feline brain are immunopositive for A beta 42 but not A beta 40. This is the first observation of nascent AD pathology in the aged feline brain. Canine plaques also contained epitopes within A beta 1(-17), A beta 17(-24), and A beta 1(-28). In all species examined, vascular deposits were immunopositive for both A beta 40 and A beta 42. In the human brain, diffuse plaques were preferentially A beta 42 immunopositive, while neuritic plaques and vascular deposits were both A beta 40 and A beta 42 immunopositive. However, not all neuritic plaques contain A beta 40 epitopes.

journal_name

Neurobiol Aging

journal_title

Neurobiology of aging

authors

Cummings BJ,Satou T,Head E,Milgram NW,Cole GM,Savage MJ,Podlisny MB,Selkoe DJ,Siman R,Greenberg BD,Cotman CW

doi

10.1016/0197-4580(96)00062-0

subject

Has Abstract

pub_date

1996-07-01 00:00:00

pages

653-9

issue

4

eissn

0197-4580

issn

1558-1497

pii

S0197458096000620

journal_volume

17

pub_type

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