Differential deposition of amyloid beta peptides in cerebral amyloid angiopathy associated with Alzheimer's disease and vascular dementia.
Haglund, Mattias LU ; Kalaria, Raj ; Slade, Janet and Englund, Elisabet LU
(2006)
In Acta Neuropathologica
111(5).
p.430-435
- Abstract
- Cerebral amyloid angiopathy (CAA) caused by deposition of amyloid beta (A beta) peptides in the cerebrovasculature, involves degeneration of normal vascular components and increases the risk of infarction and cerebral hemorrhage. Accumulating evidence suggests that sporadic CAA is also a significant contributor to cognitive decline and dementia in the elderly. However, the mechanisms by which CAA arises are poorly understood. While neuronal sources of A beta peptides are sufficient to cause CAA in transgenic mice overexpressing the amyloid precursor protein, there is reason to believe that in aging man, vascular disease modulates the disease process. To better understand CAA mechanisms in dementia, we assessed the frontal cortex of 62... (More)
- Cerebral amyloid angiopathy (CAA) caused by deposition of amyloid beta (A beta) peptides in the cerebrovasculature, involves degeneration of normal vascular components and increases the risk of infarction and cerebral hemorrhage. Accumulating evidence suggests that sporadic CAA is also a significant contributor to cognitive decline and dementia in the elderly. However, the mechanisms by which CAA arises are poorly understood. While neuronal sources of A beta peptides are sufficient to cause CAA in transgenic mice overexpressing the amyloid precursor protein, there is reason to believe that in aging man, vascular disease modulates the disease process. To better understand CAA mechanisms in dementia, we assessed the frontal cortex of 62 consecutive cases of Alzheimer's disease (AD), vascular dementia (VaD), and mixed dementia (MD) using immunohistochemistry with antibodies to A beta, smooth muscle actin and the carboxyl-terminal peptides to detect A beta(40) and A beta(42). While vascular A beta deposition was invariably associated with smooth muscle degeneration as indicated by absence of smooth muscle cell actin reactivity, VaD/MD cases exhibited markedly more vascular A beta(42) deposits and smooth muscle actin loss compared to AD cases with similar degrees of CAA and A beta(40) deposition. This suggests that distinct mechanisms are responsible for the differential deposition of A beta in CAA associated with AD and that associated with ischemic/cerebrovascular disease. It is plausible that experimental studies on the effects of cerebrovascular disease on A beta production and elimination will yield important clues on the pathogenesis of CAA. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/154458
- author
- Haglund, Mattias
LU
; Kalaria, Raj
; Slade, Janet
and Englund, Elisabet
LU
- organization
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- muscle actin, cerebrovascular disorder, smooth, congophilic angiopathy, dementia
- in
- Acta Neuropathologica
- volume
- 111
- issue
- 5
- pages
- 430 - 435
- publisher
- Springer
- external identifiers
-
- wos:000237322900004
- scopus:33646246165
- ISSN
- 1432-0533
- DOI
- 10.1007/s00401-006-0054-z
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Division V (013230900), Pathology, (Lund) (013030000)
- id
- 23844230-5d68-4f51-b902-9db2832a4afb (old id 154458)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16555084&dopt=Abstract
- date added to LUP
- 2016-04-01 16:03:54
- date last changed
- 2022-03-30 05:11:16
@article{23844230-5d68-4f51-b902-9db2832a4afb,
abstract = {{Cerebral amyloid angiopathy (CAA) caused by deposition of amyloid beta (A beta) peptides in the cerebrovasculature, involves degeneration of normal vascular components and increases the risk of infarction and cerebral hemorrhage. Accumulating evidence suggests that sporadic CAA is also a significant contributor to cognitive decline and dementia in the elderly. However, the mechanisms by which CAA arises are poorly understood. While neuronal sources of A beta peptides are sufficient to cause CAA in transgenic mice overexpressing the amyloid precursor protein, there is reason to believe that in aging man, vascular disease modulates the disease process. To better understand CAA mechanisms in dementia, we assessed the frontal cortex of 62 consecutive cases of Alzheimer's disease (AD), vascular dementia (VaD), and mixed dementia (MD) using immunohistochemistry with antibodies to A beta, smooth muscle actin and the carboxyl-terminal peptides to detect A beta(40) and A beta(42). While vascular A beta deposition was invariably associated with smooth muscle degeneration as indicated by absence of smooth muscle cell actin reactivity, VaD/MD cases exhibited markedly more vascular A beta(42) deposits and smooth muscle actin loss compared to AD cases with similar degrees of CAA and A beta(40) deposition. This suggests that distinct mechanisms are responsible for the differential deposition of A beta in CAA associated with AD and that associated with ischemic/cerebrovascular disease. It is plausible that experimental studies on the effects of cerebrovascular disease on A beta production and elimination will yield important clues on the pathogenesis of CAA.}},
author = {{Haglund, Mattias and Kalaria, Raj and Slade, Janet and Englund, Elisabet}},
issn = {{1432-0533}},
keywords = {{muscle actin; cerebrovascular disorder; smooth; congophilic angiopathy; dementia}},
language = {{eng}},
number = {{5}},
pages = {{430--435}},
publisher = {{Springer}},
series = {{Acta Neuropathologica}},
title = {{Differential deposition of amyloid beta peptides in cerebral amyloid angiopathy associated with Alzheimer's disease and vascular dementia.}},
url = {{http://dx.doi.org/10.1007/s00401-006-0054-z}},
doi = {{10.1007/s00401-006-0054-z}},
volume = {{111}},
year = {{2006}},
}