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Neurobiol Aging. 2009 Jul;30(7):1125-34. Epub 2007 Nov 14.

Synaptic proteins, neuropathology and cognitive status in the oldest-old.

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Institute of Brain Aging and Dementia, University of California, Irvine, CA 92697-4540, USA.


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.

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