The presynaptic protein, α-synuclein (α-syn), has been shown to play a crucial role in multiple neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), and dementia with Lewy bodies (DLB).
Beyond the synucleinopathies, the abnormal deposition of aSyn is frequently seen in a variety of other neurodegenerative proteinopathies including Alzheimer's disease.
With use of alpha-synuclein (AS) immunohistochemistry, LBs were detected in 74 of 131 (56.5%) of the AD + LB cases; the remaining 57 cases (43.5%) did not have LBs.
Analysis of the superior temporal cortex, a region selectively affected in LBD and AD, showed that compared to controls, levels of alpha-synuclein were increased in cases of diffuse LBD (DLBD), levels of beta-synuclein were decreased in AD and DLBD, and levels of gamma-synuclein were increased in AD cases.
Alpha synuclein also contributes to the intracellular inclusions of multiple system atrophy, and a fragment has been found in senile plaques in Alzheimer's disease.
Moreover, tau and α-synuclein concentrations showed opposite trends in AD and DLB patients, suggesting the benefit of combining the two biomarkers for differentiation of DLB from AD and controls.
Many neurodegenerative diseases are characterized by progressive loss of neurons and abnormal protein accumulation, including amyloid (A)β and tau in Alzheimer's disease and Lewy bodies and α-synuclein (α-syn) in Parkinson's disease (PD).
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.
Further investigation of alpha-synuclein and its relationship to pathological conditions promoting Lewy body formation in AD, PD, and DLB may yield further insight into pathogenesis of these diseases.
For this reason, we sought to examine the expression levels of members of the autophagy pathway in brains of patients with DLB and Alzheimer's Disease (AD) and in alpha-synuclein transgenic mice.
The cytoplasmic microtubule associated protein tau and alpha-synuclein (αS) are found in an assembled state in Alzheimer's disease and Parkinson's disease, respectively.
The present study examined concomitant pathological neuronal inclusions of TDP-43, hyperphosphorylated tau and α-synuclein protein in the anterior cingulate, hippocampus and entorhinal cortex in young (≤65 years at death) vs. elderly (≥80 years at death) cases with pathologically confirmed FTLD (n = 52) or Alzheimer's disease (AD) (n = 47).
These results show that frontal and temporal cortex in PDC is distinguished from AD and PSP by its accumulation of abnormal SNCA and suggest that PDC be considered a synucleinopathy as well as a tauopathy.
Enhanced accumulation of phosphorylated alpha-synuclein and elevated beta-amyloid 42/40 ratio caused by expression of the presenilin-1 deltaT440 mutant associated with familial Lewy body disease and variant Alzheimer's disease.
In conclusion, (1) a frontal lobe syndrome-like personality change may be one of the characteristic clinical features of early-onset CWP-AD, (2) the deposition pattern of Abeta40 and Abeta42 in CWP-AD is more variable than that of presenilin-1-linked cases, (3) Abeta deposition can result in development of dementia without tau pathology, and (4) CWP-AD with LBs and several other neurodegenerative disorders with LBs share a common process involving alpha-synuclein and NAC deposition.
SNCA gene polymorphism may be associated with an increased risk of AD and GG genotype of rs10516846 and elevated SNCA level in CSF may increase the risk of early-onset AD.