PC 3 reflects Alzheimer’s disease pathology and cognitive impairment. (A) Significant correlations (Spearman’s rank correlation) between PC 3 and all Alzheimer’s disease CSF biomarkers (Aβ42 N = 277; Aβ42/40 N = 277; p-tau/Aβ42 N = 277; p-tau181 N = 277), CSF markers of neuronal injury (NfL N = 272; t-tau N = 277), MRI measures of neurodegeneration (AD signature thickness, cortical thickness, hippocampal volume and WM hypointensities all N = 189), cognitive test scores (KOD N = 162; MMSE N = 187; MoCA N = 234; RAVLT N = 172; RCF N = 163) and age (N = 278). Units for the CSF variables are indicated in Table 1. (B) Correlations between CSF Alzheimer’s disease biomarkers and PC 3 were stratified by diagnosis [SCD N = 151 (NfL N = 147); MCI N = 60; AD N = 47 (NfL N = 46); Other N = 19]. The correlations remained significant only for some of the diagnostic groups (Supplementary Table 3B). (C) CSF Alzheimer’s disease biomarker correlations stratified by ATN category (A–T–N– N = 146; A–T–N+ N = 30; A–T+N– N = 4; A–T+N+ N = 5; A+T–N– N = 14; A+T–N+ N = 6; A+T+N– N = 47; A+T+N+ N = 20) displayed divergent relationships among the categories (Supplementary Table 3B). Only correlations with a significance level of P < 0.0001 (unadjusted) are shown and the plotted trendlines were acquired by robust linear regressions. Each data point represents a patient and is annotated by the diagnostic group or ATN category. Aβ; beta-amyloid; AD, Alzheimer's disease; ATN categories, (A) beta-amyloid, (T) p-tau, (N) neurodegeneration (+) positive or (−) negative; KOD, Digit Symbol-Coding test; MCI, mild cognitive impairment; MMSE, Mini Mental State Examination; MoCA, Montreal Cognitive Assessment; NfL, neurofilament light; Other, other dementias/amnesias; RAVLT, Rey Auditory Verbal Learning Test; RCF, Rey Complex Figure memory test; p-tau, phosphorylated tau; SCD, subjective cognitive decline; t-tau, total tau; WM, white matter.