Decreases in soluble alpha-synuclein in frontal cortex correlate with cognitive decline in the elderly.
Alpha-synuclein (ASN) is a presynaptic protein and major component of Lewy bodies. It is considered important in the pathogenesis of Alzheimer's disease (AD), but its relevance to progressive cognitive decline in aging is largely unknown. To address this issue, ASN immunoreactivity was measured in frontal cortex of elderly individuals with no cognitive impairment (NCI), mild cognitive impairment (MCI) and early AD using a Western blot technique and a polyclonal antibody to ASN. ASN immunoreactivity was significantly lower in AD than in MCI and NCI, but there was no difference between MCI and NCI. The ASN immunoreactivity correlated with CERAD diagnosis, as well as Mini-Mental State Exam (MMSE) score, global neuropsychologic z-score and some, but not all, frontal neuropsychology measures. Clinical correlations were stronger for ASN than synaptophysin immunoreactivity assessed in a similar manner. The correlation with MMSE was robust when NCI cases were considered separately, suggesting that decreases in soluble ASN may be an early feature of cognitive decline in aging and AD.
Wang
Deng-Shun
DS
Department of Pathology (Neuropathology), Mayo Clinic, Jacksonville, FL 32224, USA.
Bennett
David A
DA
Mufson
Elliott
E
Cochran
Elizabeth
E
Dickson
Dennis W
DW
D000368:Aged; D000369:Aged, 80 and over; D003072:Cognition Disorders / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D051843:Synucleins; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein