Journal Article

DZNE-2026-00001

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Association between basal forebrain volume and age in the presenilin-1 E280A autosomal dominant Alzheimer's disease kindred.

He, B. ; Ospina Lopera, P. ; Espinosa, A. ; Becerra, J. C. ; Osorio, L. ; Alzate, D. ; Alvarez, S. ; Grazia, A.DZNE* ; Teipel, S. J.DZNE* ; Malotaux, V. ; Tristão-Pereira, C. ; Rowe, M. C. ; Giudicessi, A. ; Su, Y. ; Chen, Y. ; Do Carmo, S. ; Aguillón, D. ; Cuello, A. C. ; Quiroz, Y. T.

2026
Wiley Hoboken, NJ

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Please use a persistent id in citations: doi:10.1002/alz.71052

Abstract: The basal forebrain (BF), a key cholinergic hub, undergoes atrophy in Alzheimer's disease (AD), contributing to cognitive decline. However, its age-related differences and early vulnerability in autosomal dominant AD (ADAD) remain unclear.We studied 158 individuals from the Colombian Presenilin-1 (PSEN1) E280A kindred, including 80 carriers (60 cognitively unimpaired, 20 cognitively impaired). Participants underwent structural magnetic resonance imaging, blood sampling, and neuropsychological testing. Analysis of covariance and false discovery rate-corrected t tests assessed group differences. Correlations evaluated associations among BF volume, age, and cognitive scores. Hamiltonian Markov chain Monte Carlo modeling estimated the age at which BF volume diverged between carriers and non-carriers.BF volume was comparable between cognitively unimpaired carriers and non-carriers but declined more rapidly in carriers, with divergence at ≈ 37.8 years, 6 years prior to the median age at onset of mild cognitive impairment.BF volume changes precede the onset of clinical symptoms in ADAD, supporting its potential as an early biomarker of cholinergic degeneration and therapeutic target.There were not basal forebrain (BF) volume differences between PSEN1 E280A unimpaired carriers and non-carriers. Age-related modeling revealed a faster BF volume decline in carriers vs non-carriers. Age-related differences first emerged at 37.8 years, about 6 years before clinical onset. BF volume was related to age, cognition, and plasma phosphorylated tau 217 levels. BF changes may be early indicators of Alzheimer's disease-related neurodegeneration.

Keyword(s): Humans (MeSH) ; Presenilin-1: genetics (MeSH) ; Alzheimer Disease: genetics (MeSH) ; Alzheimer Disease: pathology (MeSH) ; Alzheimer Disease: diagnostic imaging (MeSH) ; Male (MeSH) ; Female (MeSH) ; Basal Forebrain: pathology (MeSH) ; Basal Forebrain: diagnostic imaging (MeSH) ; Magnetic Resonance Imaging (MeSH) ; Middle Aged (MeSH) ; Adult (MeSH) ; Neuropsychological Tests (MeSH) ; Aged (MeSH) ; Cognitive Dysfunction: pathology (MeSH) ; Cognitive Dysfunction: genetics (MeSH) ; Colombia (MeSH) ; autosomal dominant Alzheimer's disease ; basal forebrain ; brain volume ; memory ; presenilin 1 ; Presenilin-1 ; PSEN1 protein, human

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Contributing Institute(s):

1. Clinical Dementia Research (Rostock /Greifswald) (AG Teipel)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2026

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Wiley ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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