Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
Association between basal forebrain volume and age in the presenilin-1 E280A autosomal dominant Alzheimer's disease kindred.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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He Bing, Ospina Lopera Paula, Espinosa Alejandro, Becerra Juan Camilo, Osorio Laura, Alzate Diana, Alvarez Sergio, Grazia Alice, Teipel Stefan J, Malotaux Vincent, Tristão-Pereira Catarina, Rowe Meredith C, Giudicessi Averi, Su Yi, Chen Yinghua, Do Carmo Sonia, Aguillón David, Cuello A Claudio, Quiroz Yakeel T
Аннотация
INTRODUCTION: 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.
METHODS: 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.
RESULTS: 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.
DISCUSSION: BF volume changes precede the onset of clinical symptoms in ADAD, supporting its potential as an early biomarker of cholinergic degeneration and therapeutic target.
HIGHLIGHTS: 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.
METHODS: 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.
RESULTS: 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.
DISCUSSION: BF volume changes precede the onset of clinical symptoms in ADAD, supporting its potential as an early biomarker of cholinergic degeneration and therapeutic target.
HIGHLIGHTS: 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.