Alzheimer β-amyloid peptides : Normal and abnormal localization
Takahashi, R. H. ; Nam, E. E. ; Edgar, M. and Gouras, Gunnar K. LU
(2002)
In Histology and Histopathology
17(1).
p.239-246
- Abstract
Alzheimer's disease (AD) neuropathology is characterized by accumulation of "senile" plaques (SPs) and neurofibrillary tangles (NFTs) in vulnerable brain regions. SPs are principally composed of aggregates of up to 42/43 amino acid β-amyloid (Aβ) peptides. The discovery of familial AD (FAD) mutations in the genes for the amyloid precursor protein (APP) and presenilins (PSs), all of which increase Aβ42 production, support the view that Aβ is centrally involved in the pathogenesis of AD. Aβ42 aggregates readily, and is thought to seed the formation of fibrils, which then act as templates for plaque formation. Aβ is generated by the sequential intracellular cleavage of APP by β-secretase to generate the N-terminal end of Aβ, and... (More)
Alzheimer's disease (AD) neuropathology is characterized by accumulation of "senile" plaques (SPs) and neurofibrillary tangles (NFTs) in vulnerable brain regions. SPs are principally composed of aggregates of up to 42/43 amino acid β-amyloid (Aβ) peptides. The discovery of familial AD (FAD) mutations in the genes for the amyloid precursor protein (APP) and presenilins (PSs), all of which increase Aβ42 production, support the view that Aβ is centrally involved in the pathogenesis of AD. Aβ42 aggregates readily, and is thought to seed the formation of fibrils, which then act as templates for plaque formation. Aβ is generated by the sequential intracellular cleavage of APP by β-secretase to generate the N-terminal end of Aβ, and intramembranous cleavage by γ-secretase to generate the C-terminal end. Cell biological studies have demonstrated that Aβ is generated in the ER, Golgi, and endosomal/lysosomal system. A central question involving the role of Aβ in AD concerns how Aβ causes disease and whether it is extracellular Aβ deposition and/or intracellular Aβ accumulation that initiates the disease process. The most prevalent view is that SPs are composed of extracellular deposits of secreted Aβ and that Aβ causes toxicity to surrounding neurons as extracellular SP. The recent emphasis on the intracellular biology of APP and Aβ has led some investigators to consider the possibility that intraneuronal Aβ may directly cause toxicity. In this review we will outline current knowledge of the localization of both intracellular and extracellular Aβ.
(Less)
- author
- Takahashi, R. H.
; Nam, E. E.
; Edgar, M.
and Gouras, Gunnar K.
LU
- publishing date
- 2002-02-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Alzheimer's disease, Amyloid precursor protein (APP), Beta-amyloid (Aβ), Cell biology, Neuropathology
- in
- Histology and Histopathology
- volume
- 17
- issue
- 1
- pages
- 239 - 246
- publisher
- Histology and Histopathology
- external identifiers
-
- scopus:0036165129
- pmid:11813874
- ISSN
- 0213-3911
- DOI
- 10.14670/HH-17.239
- language
- English
- LU publication?
- no
- id
- 8bcf0d63-93f2-419c-b48b-67b6648928eb
- date added to LUP
- 2020-02-20 14:39:29
- date last changed
- 2024-01-02 06:00:38
@article{8bcf0d63-93f2-419c-b48b-67b6648928eb,
abstract = {{<p>Alzheimer's disease (AD) neuropathology is characterized by accumulation of "senile" plaques (SPs) and neurofibrillary tangles (NFTs) in vulnerable brain regions. SPs are principally composed of aggregates of up to 42/43 amino acid β-amyloid (Aβ) peptides. The discovery of familial AD (FAD) mutations in the genes for the amyloid precursor protein (APP) and presenilins (PSs), all of which increase Aβ42 production, support the view that Aβ is centrally involved in the pathogenesis of AD. Aβ42 aggregates readily, and is thought to seed the formation of fibrils, which then act as templates for plaque formation. Aβ is generated by the sequential intracellular cleavage of APP by β-secretase to generate the N-terminal end of Aβ, and intramembranous cleavage by γ-secretase to generate the C-terminal end. Cell biological studies have demonstrated that Aβ is generated in the ER, Golgi, and endosomal/lysosomal system. A central question involving the role of Aβ in AD concerns how Aβ causes disease and whether it is extracellular Aβ deposition and/or intracellular Aβ accumulation that initiates the disease process. The most prevalent view is that SPs are composed of extracellular deposits of secreted Aβ and that Aβ causes toxicity to surrounding neurons as extracellular SP. The recent emphasis on the intracellular biology of APP and Aβ has led some investigators to consider the possibility that intraneuronal Aβ may directly cause toxicity. In this review we will outline current knowledge of the localization of both intracellular and extracellular Aβ.</p>}},
author = {{Takahashi, R. H. and Nam, E. E. and Edgar, M. and Gouras, Gunnar K.}},
issn = {{0213-3911}},
keywords = {{Alzheimer's disease; Amyloid precursor protein (APP); Beta-amyloid (Aβ); Cell biology; Neuropathology}},
language = {{eng}},
month = {{02}},
number = {{1}},
pages = {{239--246}},
publisher = {{Histology and Histopathology}},
series = {{Histology and Histopathology}},
title = {{Alzheimer β-amyloid peptides : Normal and abnormal localization}},
url = {{http://dx.doi.org/10.14670/HH-17.239}},
doi = {{10.14670/HH-17.239}},
volume = {{17}},
year = {{2002}},
}