α-synuclein in the pathophysiology of Alzheimer's disease
Twohig, Daniel LU
and Nielsen, Henrietta M
(2019)
In Molecular Neurodegeneration
14(1).
- Abstract
The Alzheimer's disease (AD) afflicted brain is neuropathologically defined by extracellular amyloid-β (Aβ) plaques and intraneuronal neurofibrillary tangles composed of hyperphosphorylated tau protein. However, accumulating evidence suggests that the presynaptic protein α-synuclein (αSyn), mainly associated with synucleinopathies like Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA), is involved in the pathophysiology of AD. Lewy-related pathology (LRP), primarily comprised of αSyn, is present in a majority of autopsied AD brains, and higher levels of αSyn in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment (MCI) and AD have been linked to cognitive decline. Recent... (More)
The Alzheimer's disease (AD) afflicted brain is neuropathologically defined by extracellular amyloid-β (Aβ) plaques and intraneuronal neurofibrillary tangles composed of hyperphosphorylated tau protein. However, accumulating evidence suggests that the presynaptic protein α-synuclein (αSyn), mainly associated with synucleinopathies like Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA), is involved in the pathophysiology of AD. Lewy-related pathology (LRP), primarily comprised of αSyn, is present in a majority of autopsied AD brains, and higher levels of αSyn in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment (MCI) and AD have been linked to cognitive decline. Recent studies also suggest that the asymptomatic accumulation of Aβ plaques is associated with higher CSF αSyn levels in subjects at risk of sporadic AD and in individuals carrying autosomal dominant AD mutations. Experimental evidence has further linked αSyn mainly to tau hyperphosphorylation, but also to the pathological actions of Aβ and the APOEε4 allele, the latter being a major genetic risk factor for both AD and DLB. In this review, we provide a summary of the current evidence proposing an involvement of αSyn either as an active or passive player in the pathophysiological ensemble of AD, and furthermore describe in detail the current knowledge of αSyn structure and inferred function.
(Less)
- author
- Twohig, Daniel
LU
and Nielsen, Henrietta M
- publishing date
- 2019-06-11
- type
- Contribution to journal
- publication status
- published
- keywords
- Alzheimer Disease/metabolism, Brain/metabolism, Cognitive Dysfunction/metabolism, Humans, Plaque, Amyloid/metabolism, alpha-Synuclein/metabolism, tau Proteins/metabolism
- in
- Molecular Neurodegeneration
- volume
- 14
- issue
- 1
- article number
- 23
- publisher
- BioMed Central (BMC)
- external identifiers
-
- scopus:85067174182
- pmid:31186026
- ISSN
- 1750-1326
- DOI
- 10.1186/s13024-019-0320-x
- language
- English
- LU publication?
- no
- id
- ee1923cd-82ad-478d-b103-9d2a2ae79ab9
- date added to LUP
- 2024-05-08 13:57:30
- date last changed
- 2024-06-06 06:49:23
@article{ee1923cd-82ad-478d-b103-9d2a2ae79ab9,
abstract = {{<p>The Alzheimer's disease (AD) afflicted brain is neuropathologically defined by extracellular amyloid-β (Aβ) plaques and intraneuronal neurofibrillary tangles composed of hyperphosphorylated tau protein. However, accumulating evidence suggests that the presynaptic protein α-synuclein (αSyn), mainly associated with synucleinopathies like Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA), is involved in the pathophysiology of AD. Lewy-related pathology (LRP), primarily comprised of αSyn, is present in a majority of autopsied AD brains, and higher levels of αSyn in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment (MCI) and AD have been linked to cognitive decline. Recent studies also suggest that the asymptomatic accumulation of Aβ plaques is associated with higher CSF αSyn levels in subjects at risk of sporadic AD and in individuals carrying autosomal dominant AD mutations. Experimental evidence has further linked αSyn mainly to tau hyperphosphorylation, but also to the pathological actions of Aβ and the APOEε4 allele, the latter being a major genetic risk factor for both AD and DLB. In this review, we provide a summary of the current evidence proposing an involvement of αSyn either as an active or passive player in the pathophysiological ensemble of AD, and furthermore describe in detail the current knowledge of αSyn structure and inferred function.</p>}},
author = {{Twohig, Daniel and Nielsen, Henrietta M}},
issn = {{1750-1326}},
keywords = {{Alzheimer Disease/metabolism; Brain/metabolism; Cognitive Dysfunction/metabolism; Humans; Plaque, Amyloid/metabolism; alpha-Synuclein/metabolism; tau Proteins/metabolism}},
language = {{eng}},
month = {{06}},
number = {{1}},
publisher = {{BioMed Central (BMC)}},
series = {{Molecular Neurodegeneration}},
title = {{α-synuclein in the pathophysiology of Alzheimer's disease}},
url = {{http://dx.doi.org/10.1186/s13024-019-0320-x}},
doi = {{10.1186/s13024-019-0320-x}},
volume = {{14}},
year = {{2019}},
}