Table 2.
Fluid and tissue biomarkers of AD pathology.
| Biomarker | Utility for inclusion/exclusion criteria | Utility as an outcome measure | Procedure | Comments |
|---|---|---|---|---|
| CSF Aβ, tau, pTau | DLB-AD > DLB-p: tTau/Aβ1−42 good sensitivity and specificity (2) DLB vs. AD: Aβ42/Aβ38 modest sensitivity and specificity (AUC 0.76) (28, 29) AD vs. MCI/Ctrl: core biomarkers, improve detection of early stages (30, 31) |
PD: Progression (32) DLB: Changes over time are not established DLB-AD vs. DLB-p tTau/Aβ1−42: worse progression (2–4, 33–37) AD: Prodromal / baseline Aβ and tau related to later atrophy, amyloid, decline (38–41) |
Lumbar puncture | AD: soon universal Aβ cutoffs. Timecourse data marks AD subtypes (39, 42); indicates drug-target engagement (43, 44) |
| CSF NfL | DLB: Sensitive and early marker, nonspecific (45). Elevations in DLB > Ctrl (AUC 0.94), proDLB > Ctrl (AUC 0.87), DLB > proDLB (AUC 0.6), DLB-AD > DLB-p (lower AUC vs. tau/Aβ, not shown) (46) MSA, PSP, CBS > other parkinsonian dz (45, 47) AD: sensitive, nonspecific (31) |
DLB: Changes over time are not established AD: Correlates with degeneration (48); increase with dementia, decline, atrophy (46, 49). |
Lumbar puncture | |
| Plasma Aβ42/40 | DLB: Aβ42 unchanged in small study (50); ratio not studied AD: Small effect but good AUC (~0.85), complements covariates (APOE ε4, age) | Changes over time are not established | Blood draw | AUC better for mass spec vs. IA; however stability unproven |
| Plasma tTau/pTau | DLB: Nonspecific for DLB, small study, ratio untested (50); predicts abnormal tau-PET and CSF Aβ42/Aβ40 (51) AD vs. Ctrl, NDD: pTau181 and pTau217 accurate (AUCs) (0.87 – 0.98); DLB part of NDD controls (52) |
DLB: Changes over time are not established AD: pTau181 and pTau217 predict and correlate with ongoing progression (52–54); more amyloid-specific than plasma NfL |
Blood draw | Head-to-head comparison needed |
| Plasma NfL | Nonspecific marker of damage (54, 55) DLB and proDLB vs. Ctrl: Elevated but unclear test performance (preprint) (56) |
DLB: Predicts cognitive progression (preprint) (56); changes over time not established AD: Progression independent of tau but not AD-specific (54) |
Blood draw |
Designation of “good” means >90%. AD, Alzheimer's disease; PD, Parkinson's disease; DLBs, dementia with Lewy bodies; DLB-AD, dementia with Lewy bodies and AD biomarkers; DLB-p, “DLB-pure”/dementia with Lewy bodies and lacking AD biomarkers; proDLB, prodromal DLB; MSA, multiple system atrophy; PSP, progressive supranuclear palsy; CBS, corticobasal syndrome; tTau, total tau; pTau, phosphorylated tau; NDD, neurodegenerative diseases/dementias; NfL, neurofilament light chain; AUC, area under the curve; Ctrl, controls; dz, diseases; IA, immunoassay.