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Xia C, Makaretz SJ, Caso C, McGinnis S, Gomperts SN, Sepulcre J, Gomez-Isla T, Hyman BT, Schultz A, Vasdev N, Johnson KA, Dickerson BC. Association of In Vivo [18F]AV-1451 Tau PET Imaging Results With Cortical Atrophy and Symptoms in Typical and Atypical Alzheimer Disease. JAMA Neurol. 2017 Apr 1;74(4):427-436. PubMed.
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University of Gothenburg
This is the first study to report the relationship of cortical thinning assessed with structural MRI and hyperphosphorylated tau pathology measured with [18F]AV-1451. The main findings, namely the differential patterns of AV-1451 uptake in AD variants and the strong spatial overlap of cortical atrophy and brain regions affected by tau pathology, are confirming previous results (e.g. Ossenkoppele et al., 2016) where neuronal dysfunction/neurodegeneration was assessed using FDG PET rather than MRI.
The study generally strongly confirms previous findings from both neuropathology and neuroimaging studies, strengthening the knowledge that tau pathology is closely related to measures of neurodegeneration—more closely than is Aβ pathology.
Despite the small sample sizes in most published studies, the reproducibility of findings using tau PET is striking and sends a very encouraging signal to the biomarker community. It is noteworthy, however, that all patients in the current study, including the amnesic AD patients, are rather young, representing early onset AD, and we have found that these differ from late-onset AD both in AV1451 uptake and cortical atrophy pattern.
One finding that is not commented on in detail is that regions affected by tau pathology generally seem larger than atrophic regions, raising the question whether tau pathology occurs before neurons become dysfunctional or perish.
It is obviously difficult to draw strong conclusions from such a small sample but the present findings, combined with the knowledge gleaned especially during the past three years, support the idea that in vivo tau burden, as seen in these scans, is a valid marker for clinical symptoms and neurodegeneration in AD.
With obvious interplay between amyloid and tau pathology, the latter seems to be driven by the former, so it is not one or the other that is most important, but rather knowing when and where each pathology occurs. In this regard, PET scans are, and will continue to be, extremely valuable tools for both identifying suitable candidates for treatment trials and as outcome measures.
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.
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