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

Abstract

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.

The Nun Study

“…29 The other study reported that in the frontal cortex of old-older normal controls with AD pathology, equivalent to our ASYMAD group, synaptophysin, a presynaptic marker, is enhanced. 30 An alternative explanation, based on functional neuroimaging studies, 31,32 could be that in ASYMAD, some neurons and circuits are irreversibly damaged by AD pathology, and different and compensatory circuits become operative based on different stages of disease. Consequently, the circuitry of the cerebral Figure 1 Cell body, nuclear, and nucleolar markers for morphometric measurements (A) Large coronal section of a formalin-fixed brain of a control subject (left hemisphere).…”

Neural reserve, neuronal density in the locus ceruleus, and cognitive decline

“…) or their components (synapses 8,9 ) in key locations. This approach allows collection of neuronal and pathologic data from the same brain regions, facilitating examination of their conjoint correlations with cognition.…”

APOE ε2 Allele Is Associated with Larger Regional Cortical Thicknesses and Volumes

“…Several possible mechanisms have been considered, such as relatively intact synaptic integrity [36] , larger brain size [7] and higher efficiency in clearing soluble ␤ -amyloid relative to 4 [37,38] . The latter possible mechanism is helpful in explaining the difference in MRI measures between the 2 and 4 carriers.…”