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Cited by 146

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Progression of Cerebral Amyloid Angiopathy: Accumulation of Amyloid-ß40 in Affected Vessels

Alonzo, Norma C., Hyman, Bradley T., Rebeck, G William, Greenberg, Steven M.·1998·Journal of Neuropathology and Experimental Neurology
DOI 10.1097/00005072-199804000-00008
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Abstract

Cerebrovascular deposits of amyloid (cerebral amyloid angiopathy, or CAA) are generally asymptomatic, but in advanced cases, they can lead to vessel rupture and hemorrhage. The process of progression in CAA was studied by comparison of postmortem brains with asymptomatic ("mild") CAA to brains with the form of the disease associated with hemorrhage ("severe CAA"). Cortical and meningeal vessels were immunostained for beta-amyloid and examined by confocal microscopy and by systematic quantitative sampling. We focused on 2 quantitative parameters: the proportion of vessels affected by amyloid (a measure of amyloid seeding of vessels) and the amount of amyloid per affected vessel (a measure of growth of existing lesions). Surprisingly, there was no difference between the proportion of affected cortical vessels in mild and severe CAA (0.29 vs 0.32, p = 0.65), but rather an increase in the area of the 40 amino acid form of beta-amyloid per affected cortical vessel (198.5 +/- 38.7 vs 455.8 +/- 100.9 microm2/vessel, p < 0.007). Increasing doses (from 0 to 1 to 2 copies) of the apolipoprotein E epsilon4 allele were also associated with greater amyloid per vessel without change in the proportion of affected vessels within each class of CAA severity. These findings suggest that progression from asymptomatic to advanced CAA reflects progressive accumulation of amyloid in vessels previously seeded with amyloid, and that this process is selectively enhanced by apolipoprotein E epsilon4.

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  • Pathologically elevated BACE1 expression in these cells has been implicated in the development of metabolic diseases, including type 2 diabetes, obesity, and cardiovascular disease.

    “Pathologically elevated BACE1 expression in these cells has been implicated in the development of metabolic diseases, including type 2 diabetes, obesity, and cardiovascular disease.”

    From BACE1: More than just a β‐secretase (2022) · cites this paper as [40]

  • In a variety of pathological conditions, including AD, cerebral amyloid angiopathy, and metabolic diseases such as type 2 diabetes and obesity, BACE1 expression and activity are increased and drive disease progression.

    “In a variety of pathological conditions, including AD, cerebral amyloid angiopathy, and metabolic diseases such as type 2 diabetes and obesity, BACE1 expression and activity are increased and drive disease progression.”

    From BACE1: More than just a β‐secretase (2022) · cites this paper as [40]

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Metadata

Authors
Alonzo, N. C., Hyman, B. T., Rebeck, G. W., & Greenberg, S. M.
Venue
Journal of Neuropathology and Experimental Neurology
Publisher
Oxford University Press (OUP)
Published
1998-04
Volume
57
Issue
4
Pages
353-359
ISSN
0022-3069
DOI
10.1097/00005072-199804000-00008
Cited by
146
References
0
Language
en

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