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This study was funded by the Spanish Ministry of Economy and Competitiveness (PSI2015-68793-C3-1-R and RTI2018-098762-B-C31), by Instituto de Salud Carlos III (ISCIII) through the project "PI20/00937" and co-funded by the European Union; the GAIN, Axencia Galega de Innovacion, IN607B2021/12 co-funded by the European Union, and Programa INVESTIGO, TR349V-2022-10000052-00 cofunded by the European Union. Complimentary, it was supported by predoctoral grants by the Spanish Ministry of Universities (FPU18/05768 and FPU18/00517) to AN and MCG, respectively, and (PRE2019-087612) to AGC; as well as a postdoctoral fellowship by the Spanish Ministry of Science and Innovation (FJC2020-046183-I) to JdFL.

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Longitudinal changes in the functional connectivity of individuals at risk of Alzheimer's disease

Publicat a:Geroscience. 46 (3): 2989-3003 - 2024-06-01 46(3), DOI: 10.1007/s11357-023-01036-5

Autors: García-Colomo, A; Nebreda, A; Carrasco-Gómez, M; de Frutos-Lucas, J; Ramirez-Toraño, F; Spuch, C; Comis-Tuche, M; Bruña, R; Alfonsín, S; Maestú, F

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First-degree relatives of Alzheimer's disease patients constitute a key population in the search for early markers. Our group identified functional connectivity differences between cognitively unimpaired individuals with and without a family history. In this unprecedented follow-up study, we examine whether family history is associated with a longitudinal increase in the functional connectivity of those regions. Moreover, this is the first work to correlate electrophysiological measures with plasma p-tau231 levels, a known pathology marker, to interpret the nature of the change. We evaluated 69 cognitively unimpaired individuals with a family history of Alzheimer's disease and 28 without, at two different time points, approximately 3 years apart, including resting state magnetoencephalography recordings and plasma p-tau231 determinations. Functional connectivity changes in both precunei and left anterior cingulate cortex in the high-alpha band were studied using non-parametric cluster-based permutation tests. Connectivity values were correlated with p-tau231 levels. Three clusters emerged in individuals with family history, exhibiting a longitudinal increase of connectivity. Notably, the clusters for both precunei bore a striking resemblance to those found in previous cross-sectional studies. The connectivity values at follow-up and the change in connectivity in the left precuneus cluster showed significant positive correlations with p-tau231. This study consolidates the use of electrophysiology, in combination with plasma biomarkers, to monitor healthy individuals at risk of Alzheimer's disease and emphasizes the value of combining noninvasive markers to understand the underlying mechanisms and track disease progression. This could facilitate the design of more effective intervention strategies and accurate progression assessment tools.

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