Synaptic loss in Alzheimer's disease and other dementias

TLDR

The extent and location of neuronal losses necessary or sufficient to produce dementia in patients with Alzheimer’s Disease is unknown. The study aimed to determine the synaptic terminal loss underlying dementia by examining postmortem brain tissue. Immunohistochemistry with synapsin I and synaptophysin antibodies and quantitative microscopy measured synaptic density in hippocampal complexes of eight AD patients and eight controls. AD patients exhibited a marked reduction of synaptic staining in the outer half of the dentate gyrus molecular layer, with a slight increase in the inner half, and similar depletion was observed in a non‑AD degenerative dementia case.

Abstract

The extent and location of neuronal losses necessary or sufficient to produce dementia in patients with Alzheimer9s Disease (AD) is unknown. To approach this question, we studied synaptic terminals in postmortem brain tissue utilizing immunohistochemical techniques. We used antibodies against two proteins found in synaptic terminals—synapsin I and synaptophysin—as synaptic markers in the hippocampal complexes of eight patients with autopsy-proven AD and eight nondemented control subjects. Quantitative microscopy measured the regional density of synaptic staining. All AD patients showed a striking decrease in synaptic staining in the outer half of the molecular layer of the dentate gyrus compared with control brains, where the density of synaptic terminals was uniform throughout. In an additional patient with progressive degenerative dementia but without plaques or tangles on neuropathologic examination, similar depletion of synaptic staining was seen in the dentate gyrus. Quantitative densitometric analyses confirmed the focal decrease in synaptic staining in the outer half of the molecular layer in demented patients. We also found a slight increase in synaptic staining in the inner half of this layer.