Prosser, Lloyd;
Sudre, Carole H;
Oxtoby, Neil P;
Young, Alexandra L;
Malone, Ian B;
Manning, Emily N;
Pemberton, Hugh;
... Barnes, Josephine; + view all
(2024)
Biomarker pathway heterogeneity of amyloid-positive individuals.
Alzheimer's & Dementia
, 20
(12)
pp. 8503-8515.
10.1002/alz.14287.
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Abstract
INTRODUCTION: In amyloid-positive individuals, disease-related biomarker heterogeneity is understudied. METHODS: We used Subtype and Stage Inference (SuStaIn) to identify data-driven subtypes among cerebrospinal fluid (CSF) amyloid beta (1-42)–positive individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNIGO/2 [n = 376]). Variables included: CSF phosphorylated tau (p-tau181), hippocampal and whole-brain volume, logical memory (LM), composite Trail Making Test score, and white matter hyperintensity (WMH) volumes. CSF amyloid-negative, apolipoprotein E ε4 non-carrier cognitively unimpaired controls (n = 86) were used to calculate z scores. RESULTS: One subtype (n = 145) had early LM changes, with later p-tau and WMH changes. A second subtype (n = 88) had early WMH changes, were older, and more hypertensive. A third subtype (n = 100) had early p-tau changes, and reflected typical Alzheimer's disease. Some amyloid positive (n = 43) individuals were similar to the amyloid-negative group. DISCUSSION: This work identified heterogeneity in individuals who are conventionally considered homogeneous, which is likely driven by co-pathologies including cerebrovascular disease.
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