Loss of synaptophysin-like immunoreactivity in the hippocampal formation is an early phenomenon in alzheimer's disease

doi:10.1016/0306-4522(94)00422-2

Neuroscience

Volume 64, Issue 2, January 1995, Pages 375-384

https://doi.org/10.1016/0306-4522(94)00422-2 Get rights and content

Abstract

We studied a synaptophysin-like immunoreactivity in the hippocampal formation of patients with definite Alzheimer's disease, multi-infarct dementia, patients with no evidence of clinical dementia with neuropathological findings fulfilling the criteria of possible Alzheimer's disease, and age-matched nondemented controls. Possible Alzheimer's disease cases were of special interest because they were considered to represent early Alzheimer's disease. We also studied the spatial relationship of synaptophysin-like immunopositivity with amyloid-β-protein immunopositive senile plaques and anti-paired helical filament immunopositive degenerating neurons locally as well as considering the intrinsic circuits in the hippocampal formation. The synaptophysin-like immunoreactivity was decreased in the hippocampus and the entorhinal cortex in patients with definite and possible Alzheimer's disease but not in multi-infarct dementia patients compared to controls.

Equal loss of synapses in possible and definite Alzheimer's disease patients supports the hypothesis that synaptic loss is an early phenomenon in Alzheimer's disease. Unchanged synaptophysin-like immunopositivity in patients with multi-infarct dementia suggests that the loss of synapses is centrally involved in the pathogenesis of Alzheimer's disease and not dementiaper se. There was no spatial correlation between loss of synapses and amyloid-β-protein positive senile plaques. Moreover, we could not find a strict spatial relationship between senile plaques and degenerating neurons. Our results do not support the amyloid cascade hypothesis of Alzheimer's disease that local accumulation of amyloid-β-protein leads to the loss of synapses.

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Loss of synaptophysin-like immunoreactivity in the hippocampal formation is an early phenomenon in alzheimer's disease

Abstract

Neurobiol. Aging

Neurobiol. Aging

J. Psychiat. Res.

Neurobiol. Aging

Neurobiol. Aging

Neurosci. Lett.

Neurobiol. Aging

Brain Res.

Neurobiol. Aging

Brain Res.

Memory: anatomical organization of candidate brain regions

The spatial pattern of plaques and tangles in Alzheimer's disease do not support the “cascade hypothesis”

Dementia

Cholinergic fiber loss occurs in the absence of synaptophysin depletion in Alzheimer's disease primary visual cortex

Neurosci. Lett.

Synapse loss in frontal cortex biopsies in Alzheimer's disease: correlation with cognitive severity

Ann. Neurol.

EM study of the numbers of cortical synapses in the brains of ageing people and people with Alzheimer-type dementia

Acta Neuropathol. (Berl.)

The isolation of a relatively specific paired helical filament antibody

Soc. Neurosci. Abstr.

Synaptic loss in Alzheimer's disease and other dementias

Neurology