In vivo data‐driven patterns of Tau accumulation associated with AD progression using 18F‐MK‐6240 PET
Vladimir S Fonov, Tahnia Nazneen, Pedro Rosa‐Neto, D Louis Collins- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Geriatrics and Gerontology
- Neurology (clinical)
- Developmental Neuroscience
- Health Policy
- Epidemiology
Abstract
Background
Alzheimer’s disease is a neurodegenerative disease associated with accumulation of amyloid beta and tau neurofibrillary tangles following a pattern known as Braak stages (Braak 1995,2011). Recent papers (Pascoal 2020) indicate possibility to recapitulate Braak histo‐pathological stages in vivo using tau tangles PET tracer 18F‐MK‐6240, using manually defined regions of interest. This study analyzes patterns of Tau accumulation associated with AD in a completely data‐driven fashion.
Method
We used T1w MRI and 18F‐MK‐6240 Pet scans from healthy controls in the community or outpatients at the McGill University Research Centre for Studies in Aging. The following number of datasets from each diagnostic group [n scans total (m unique participants)]: cognitively normal: 347(194), mild cognitive impairment: 163(99), Alzheimer’s disease dementia: 114(77). T1w MRIs were pre‐processed (non‐uniformity correction, intensity normalization, stereotaxic registration, brain masking, tissue classification); FALCON (Fonov 2020) was used to extract the mid‐cortical surface. PET scans were linearly registered to the T1w MRI and the standardized uptake value ratio (SUVR) was calculated using whole cerebellum grey matter as the reference. SUVR values were sampled along cortical mid‐surfaces and geodesically smoothed with a 10mm gaussian and resampled to the cortical surface of MNI2009c template (Fonov 2011).
Result
Figure 1 shows Mean SUVR values on top of Figure 1, and latent factors at the bottom. Overall low values of tau in the temporal, partial and occipital region are associated with normal cognition (F1). Tau changes in the temporal lobe (F2, similar to stage 1&2) are associated with a slight cognitive change. Change in parietal and posterior temporal areas (F3, similar to stage 3&4) are associated with even more cognitive loss. Finally changes in the motor strip and ventral portion of the occipital lobe and remaining cortex (F4 and F5) are associated with the very advanced stages (5&6) of cognitive decline.
Conclusion
We discovered patterns of tau accumulation associated with progression of cognitive decline in a completely data‐driven fashion.