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Pontecorvo MJ, Devous MD, Kennedy I, Navitsky M, Lu M, Galante N, Salloway S, Doraiswamy PM, Southekal S, Arora AK, McGeehan A, Lim NC, Xiong H, Truocchio SP, Joshi AD, Shcherbinin S, Teske B, Fleisher AS, Mintun MA. A multicentre longitudinal study of flortaucipir (18F) in normal ageing, mild cognitive impairment and Alzheimer's disease dementia. Brain. 2019 Jun 1;142(6):1723-1735. PubMed.
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UCSF
This study contributes important data on longitudinal tau PET changes across a large sample of individuals spanning the AD continuum from preclinical to dementia. The data provide additional support for a strong, longitudinal relationship between tau and changes in cognition, which further establishes tau PET as an important outcome measure in clinical trials. Interestingly, baseline tau measures were found to be highly correlated with both the degree and distribution of longitudinal tau PET changes, which will be important to consider in the design of future studies and drug trials.
The paper also contributes to the emerging story regarding patients with sporadic early onset AD, who have been shown by numerous groups to have much higher baseline tau and perhaps more rapid tau accumulation than patients with late-onset disease (Ossenkoppele et al., 2016; Schöll et al., 2017; Whitwell et al., 2019).
The recently launched, multisite Longitudinal Early-Onset AD Study (LEADS) will provide further insights into this important subpopulation of AD patients, who in my opinion have something very fundamental to teach us about disease pathophysiology.
References:
Ossenkoppele R, Schonhaut DR, Schöll M, Lockhart SN, Ayakta N, Baker SL, O'Neil JP, Janabi M, Lazaris A, Cantwell A, Vogel J, Santos M, Miller ZA, Bettcher BM, Vossel KA, Kramer JH, Gorno-Tempini ML, Miller BL, Jagust WJ, Rabinovici GD. Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer's disease. Brain. 2016 May;139(Pt 5):1551-67. Epub 2016 Mar 8 PubMed.
Schöll M, Ossenkoppele R, Strandberg O, Palmqvist S, Swedish BioFINDER study, Jögi J, Ohlsson T, Smith R, Hansson O. Distinct 18F-AV-1451 tau PET retention patterns in early- and late-onset Alzheimer's disease. Brain. 2017 Sep 1;140(9):2286-2294. PubMed.
Whitwell JL, Martin P, Graff-Radford J, Machulda MM, Senjem ML, Schwarz CG, Weigand SD, Spychalla AJ, Drubach DA, Jack CR Jr, Lowe VJ, Josephs KA. The role of age on tau PET uptake and gray matter atrophy in atypical Alzheimer's disease. Alzheimers Dement. 2019 May;15(5):675-685. Epub 2019 Mar 8 PubMed.
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