Synaptic proteins, neuropathology and cognitive status in the oldest-old.
An increasing number of individuals in our population are surviving to over 90 years and a subset is at risk for developing dementia. However, senile plaque and neurofibrillary tangle pathology do not consistently differentiate individuals with and without dementia. Synaptic protein loss is a feature of aging and dementia and may dissociate 90+ individuals with and without dementia. Synaptophysin (SYN), postsynaptic density 95 (PSD-95) and growth-associated protein 43 (GAP-43) were studied in the frontal cortex of an autopsy series of 32 prospectively followed individuals (92-105 years) with a range of cognitive function. SYN protein levels were decreased in individuals with dementia and increased in those with clinical signs of cognitive impairment insufficient for a diagnosis of dementia. SYN but neither PSD-95 nor GAP-43 protein levels were significantly correlated with mini-mental status examination (MMSE) scores. Frontal cortex SYN protein levels may protect neuronal function in oldest-old individuals and reflect compensatory responses that may be involved with maintaining cognition.
Head
Elizabeth
E
Institute of Brain Aging and Dementia, University of California, Irvine, CA 92697-4540, USA. ehead@uci.edu
Corrada
Maria M
MM
Kahle-Wrobleski
Kristin
K
Kim
Ronald C
RC
Sarsoza
Floyd
F
Goodus
Matthew
M
Kawas
Claudia H
CH
D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism* / Q000473:pathology / Q000523:psychology; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D003072:Cognition Disorders / Q000378:metabolism* / Q000473:pathology / Q000523:psychology; D015331:Cohort Studies; D003704:Dementia / Q000378:metabolism* / Q000473:pathology / Q000523:psychology; D018450:Disease Progression; D000076122:Disks Large Homolog 4 Protein; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism* / Q000473:pathology; D019922:GAP-43 Protein / Q000032:analysis / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism; D009483:Neuropsychological Tests; D011446:Prospective Studies; D013570:Synaptic Membranes / Q000378:metabolism; D016708:Synaptophysin / Q000032:analysis / Q000378:metabolism*
D015415:Biomarkers; C501444:DLG4 protein, human; D000076122:Disks Large Homolog 4 Protein; D019922:GAP-43 Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016708:Synaptophysin