SV2A PET Shows Hippocampal Synaptic Loss in Cognitively Unimpaired APOE ε4/ε4 Homozygotes

Overview

Journal Alzheimers Dement

Specialties Neurology
Psychiatry

Date 2024 Oct 30

PMID 39475191

Authors

Anniina Snellman

Jouni Tuisku

Mikko Koivumaki

Saara Wahlroos

Richard Aarnio

Johan Rajander

Mira Karrasch

Laura L Ekblad

Juha O Rinne

Affiliations

Soon will be listed here.

Abstract

Introduction: We investigated hippocampal synaptic density using synaptic vesicle 2A positron emission tomography (PET), and its association with amyloid beta (Aβ) and cognitive performance in healthy apolipoprotein E (APOE) ε4 carriers.

Methods: Synaptic density was assessed in 46 individuals (APOE ε4/ε4 n = 14; APOE ε3/ε4 n = 16; APOE ε3/ε3 n = 16) with [C]UCB-J-PET standardized uptake value ratios (SUVRs), by using the centrum semiovale as a reference region. Differences in hippocampal [C]UCB-J SUVRs were analyzed with analysis of variance (ANOVA) and linear models. Associations among [C]UCB-J SUVR, Aβ, hippocampal volume, and cognitive variables were analyzed with Spearman correlation.

Results: Hippocampal synaptic density was different among the APOE groups (P= 0.016): APOE ε4/ε4 carriers had lower [C]UCB-J SUVRs compared to APOE ε3/ε3 (p = 0.013). Hippocampal synaptic density did not correlate with Consortium to Establish a Registry for Alzheimer's Disease (CERAD) total score (rho = -0.052, p = 0.74), Alzheimer's Prevention Initiative Preclinical Cognitive Composite (APCC) score (rho = 0.17, p = 0.28), or [C]PiB uptake (rho = -0.10, p = 0.50).

Discussion: Hippocampal synaptic loss emerges early in the AD continuum and is measurable in vivo in cognitively unimpaired high-risk individuals.

Highlights: Synaptic density was studied in vivo in healthy older adults using [C]UCB-J positron emission tomography. Apolipoprotein E (APOE) ε4/ε4 carriers had lower hippocampal synaptic density compared to APOE ε3/ε3. Synaptic density was not associated with cognitive performance in this population. Hippocampal synaptic alterations occur before clinical symptoms in APOE ε4/ε4 carriers.

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PMID: 39903109 PMC: 11831164. DOI: 10.1073/pnas.2416042122.

SV2A PET shows hippocampal synaptic loss in cognitively unimpaired APOE ε4/ε4 homozygotes.

Snellman A, Tuisku J, Koivumaki M, Wahlroos S, Aarnio R, Rajander J Alzheimers Dement. 2024; 20(12):8802-8813.

PMID: 39475191 PMC: 11667521. DOI: 10.1002/alz.14327.

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