Amyloid is associated with accelerated atrophy in cognitively unimpaired individuals

Alzheimers Dement (Amst). 2025 Feb 24;17(1):e70089. doi: 10.1002/dad2.70089. eCollection 2025 Jan-Mar.

ABSTRACT

INTRODUCTION: This study examined the association of longitudinal atrophy with baseline cerebrospinal fluid (CSF) amyloid beta (Aβ, A) and phosphorylated tau (p-tau, T) biomarkers (Aβ42/40, p-tau181) in 406 cognitively unimpaired (CU) individuals (6.670 years of follow-up on average, up to 13 imaging visits) to assess whether A+ is associated with Alzheimer's disease-like atrophy and whether this depends on p-tau181 levels.

METHODS: An A-T- CU group free from abnormal neurodegeneration (N) was identified using a robust normative approach and used to model normal age-related atrophy via z-scoring. Linear mixed-effects models tested differences in longitudinal atrophy between A+ and A-T-N- individuals and between A/T subgroups.

RESULTS: A+ was associated with worse atrophy within and beyond the medial temporal lobe, even at low levels of p-tau181.

DISCUSSION: Neurodegeneration likely begins soon after the onset of abnormal Aβ pathology. Clinical intervention at the earliest signs of Aβ pathology may be needed to mitigate further neurodegeneration.

HIGHLIGHTS: An A-T-N- control group was identified using a robust normative approachA+ was associated with accelerated atrophy in cognitively unimpaired individualsAtrophy was observed even at low p-tau181 levels.

PMID:39996035 | PMC:PMC11848556 | DOI:10.1002/dad2.70089