OBJECTIVE

To investigate the association between discordant β-amyloid (Aβ) PET and CSF biomarkers at baseline and the emergence of tau pathology 5 years later.

METHODS

We included 730 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants without dementia (282 cognitively normal, 448 mild cognitive impairment) with baseline [F]florbetapir PET and CSF Aβ available. Aβ CSF/PET status was determined at baseline using established cutoffs. Longitudinal data were available for [F]florbetapir (Aβ) PET (baseline to 4.3 ± 1.9 years), CSF (p)tau (baseline to 2.0 ± 0.1 years), cognition (baseline to 4.3 ± 2.0 years), and [F]flortaucipir (tau) PET (measured 5.2 ± 1.2 years after baseline to 1.6 ± 0.7 years later). We used linear mixed modeling to study the association between Aβ CSF/PET status and tau pathology measured in CSF or using PET. We calculated the proportion of CSF+/PET- participants who during follow-up (1) progressed to Aβ CSF+/PET+ or (2) became tau-positive based on [F]flortaucipir PET.

RESULTS

Aβ CSF+/PET+ (n = 318) participants had elevated CSF (p)tau levels and worse cognitive performance at baseline, while CSF+/PET- (n = 80) participants were overall similar to the CSF-/PET- (N = 306) group. Five years after baseline, [F]flortaucipir PET uptake in the CSF+/PET- group (1.20 ± 0.13) did not differ from CSF-/PET- (1.18 ± 0.08, = 0.69), but was substantially lower than CSF+/PET+ (1.48 ± 0.44, < 0.001). Of the CSF+/PET- participants, 21/64 (33%) progressed to Aβ CSF+/PET+, whereas only one (3%, difference < 0.05) became tau-positive based on [F]flortaucipir PET.

CONCLUSIONS

Aβ load detectable by both CSF and PET seems to precede substantial tau deposition. Compared to participants with abnormal Aβ levels on both PET and CSF, the CSF+/PET- group has a distinctly better prognosis.