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Ann N Y Acad Sci. 1993 Sep 24;695:59-64.

Synaptic pathology of Alzheimer's disease.

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1
Research Unit for Experimental Neuropathology, University of Vienna, Austria.

Abstract

Prospective clinico-pathological studies on dementia in Alzheimer's disease (AD), performed during the past decades, revealed a relatively poor correlation between the degree of clinical deficit and the severity of the typical neuropathological lesions of AD, the amyloid plaques and the neurofibrillary tangles. More recent data, obtained by electron microscopy, immunocytochemical as well as immunochemical techniques indicate that synaptic loss may be a better structural correlate of dementia than other brain lesions. Synaptic pathology is reflected by a loss of all major components of small synaptic vesicles and most peptides, stored in large dense cored vesicles. The significant increase of chromogranin A proprotein, a major component of large dense cored vesicles, may rather represent a defect of protein processing than preservation of a specific synaptic subpopulation. Within the brain of AD patients, the degree of synaptic loss is uneven. Most prominent reduction of synapses is found in the outer parts of the dentate gyrus molecular layer, possibly reflecting the destruction of neurons, located in the layer 2 of the entorhinal cortex. However, within the neocortex, no preferential loss of synapses in any of the cortical layers has been found. Cerebral amyloid deposition in diffuse plaques has little effect on synapse density and structure. However, within the dense amyloid core of a classical plaque, synapses are completely lost. In the surrounding neuritic portion of the plaques, synaptophysin reactivity is frequently increased, due to enlargement of synaptic boutons and to accumulation of synaptophysin in dystrophic axons. Although the reason for synapse loss in AD is yet unknown, most results suggest that it may reflect degeneration of neurons, projecting into the respective cortical areas.

[Indexed for MEDLINE]

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