A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä

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




TekijätSnellman, Anniina; Tuisku, Jouni; Koivumäki, Mikko; Wahlroos, Saara; Aarnio, Richard; Rajander, Johan; Karrasch, Mira; Ekblad, Laura L.; Rinne, Juha O.

KustantajaWILEY

KustannuspaikkaHOBOKEN

Julkaisuvuosi2024

JournalAlzheimer's and Dementia

Tietokannassa oleva lehden nimiALZHEIMERS & DEMENTIA

Lehden akronyymiALZHEIMERS DEMENT

Vuosikerta20

Numero12

Aloitussivu8802

Lopetussivu8813

Sivujen määrä12

ISSN1552-5260

eISSN1552-5279

DOIhttps://doi.org/10.1002/alz.14327

Verkko-osoitehttps://doi.org/10.1002/alz.14327

Rinnakkaistallenteen osoitehttps://research.utu.fi/converis/portal/detail/Publication/459263884


Tiivistelmä

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 [11C]UCB-J-PET standardized uptake value ratios (SUVRs), by using the centrum semiovale as a reference region. Differences in hippocampal [11C]UCB-J SUVRs were analyzed with analysis of variance (ANOVA) and linear models. Associations among [11C]UCB-J SUVR, Aβ, hippocampal volume, and cognitive variables were analyzed with Spearman correlation.

Results: Hippocampal synaptic density was different among the APOE groups (PANOVA = 0.016): APOE ε4/ε4 carriers had lower [11C]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 [11C]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 [11C]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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Julkaisussa olevat rahoitustiedot
A.S. reports funding from the Finnish Governmental Research Funding (VTR) for Turku University Hospital for the ASIC-E4 study. A.S. received additional personal grants from the Research Council of Finland (grant number 341059), the Emil Aaltonen Foundation, the Paulo Foundation, and the Orion Research Foundation sr directly related to this study. L.L.E. was financially supported by the Paulo Foundation, the Emil Aaltonen Foundation, and Finnish Governmental Research Funding (VTR). J.O.R. received funding from the Sigrid Juselius Foundation and the Finnish Governmental Research Funding (VTR) for Turku University Hospital.


Last updated on 2025-24-02 at 13:59