Biomarker pathway heterogeneity of amyloid-positive individuals
Lloyd Prosser1, Carole H Sudre1,2,3,4, Neil P Oxtoby3
1Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, Queen Square, London, UK.
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.
Highlights:
Data-driven modeling identified marker heterogeneity in amyloid-positive individuals. Heterogeneity reflected Alzheimer's disease-like, vascular-like, and mixed pathology presentations. Some amyloid-positive individuals were more similar to amyloid-negative controls. Vascular pathology plays a key role in understanding heterogeneity in those on the amyloid pathway.
