Synaptic alterations in CA1 in mild Alzheimer disease and mild cognitive impairment

TLDR

Synapse loss and reduced stratum radiatum volume are early structural changes in mild Alzheimer disease, positioning mild cognitive impairment as a transitional stage toward dementia. The study aimed to quantify synapse numbers in the CA1 stratum radiatum of mild Alzheimer disease, mild cognitive impairment, and cognitively normal individuals to assess whether synapse loss occurs early in disease progression. Synapse counts were obtained from postmortem hippocampal tissue using an unbiased stereologic sampling scheme combined with transmission electron microscopy. mAD subjects exhibited a 55% reduction in CA1 synapses compared to controls, MCI subjects had an 18% lower count, synapse numbers correlated with memory performance, but showed no association with Braak stage or APOE genotype, supporting early synaptic loss as a marker of cognitive decline.

Abstract

To evaluate the total number of synapses in the stratum radiatum (str rad) of the human hippocampal CA1 subfield in individuals with mild Alzheimer disease (mAD), mild cognitive impairment (MCI), or no cognitive impairment (NCI) and determine if synapse loss is an early event in the progression of the disease.Short postmortem autopsy tissue was obtained, and an unbiased stereologic sampling scheme coupled with transmission electron microscopy was used to directly visualize synaptic contacts.Individuals with mAD had fewer synapses (55%) than the other two diagnostic groups. Individuals with MCI had a mean synaptic value that was 18% lower than the NCI group mean. The total number of synapses showed a correlation with several cognitive tests including those involving both immediate and delayed recall. Total synaptic numbers showed no relationship to the subject's Braak stage or to APOE genotype. The volume of the str rad was reduced in mAD vs the other two diagnostic groups that were not different from each other.These results strongly support the concept that synapse loss is a structural correlate involved very early in cognitive decline in mild Alzheimer disease (mAD) and supports mild cognitive impairment as a transitional stage between mAD and no cognitive impairment.