TY - JOUR
T1 - Atypical Alzheimer’s disease phenotypes with normal or borderline PET biomarker profiles
AU - Singh, Neha Atulkumar
AU - Graff-Radford, Jonathan
AU - Machulda, Mary M.
AU - Schwarz, Christopher G.
AU - Baker, Matthew C.
AU - Rademakers, Rosa
AU - Ertekin-Taner, Nilufer
AU - Lowe, Val J.
AU - Josephs, Keith A.
AU - Whitwell, Jennifer L.
N1 - Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.
PY - 2022/12
Y1 - 2022/12
N2 - Posterior cortical atrophy (PCA) and logopenic progressive aphasia (LPA) are clinical syndromes that commonly have underlying Alzheimer’s disease (AD), although non-AD pathologies have also been reported. PET imaging allows for identification of beta-amyloid (Aβ) and tau in AD, so we aimed to assess these in a large cohort to identify patients that do not have evidence for biomarker-defined AD. Eight-one patients, 47 PCA and 34 LPA, underwent extensive neurological and neuropsychological testing, [11C] Pittsburgh compound B, [18F] flortaucipir and [18F] fluorodeoxyglucose PETs. Global Aβ and tau-PET standardized uptake value ratios (SUVRs) were plotted for all patients and outliers, and patients with abnormally low SUVRs compared to the biomarker-classic cohort were identified. Six (7.4%) biomarker-outlier cases were identified, and three patterns were observed: (i) negative/borderline Aβ-PET and striking widespread tau-PET uptake (two LPA); (ii) negative/borderline Aβ-PET and low tau-PET uptake (three PCA) and (iii) elevated Aβ-PET uptake but mild focal tau-PET uptake (one LPA). Among the unusual patients in group ii, two patients showed no abnormal tau uptake suggesting non-AD pathology, with one developing features of cortico-basal syndrome and the other dementia with Lewy bodies. The remaining patient showed very mild focal tau uptake. This study demonstrates that a small minority (~ 8%) of PCA and LPA patients do not show the typical striking patterns of Aβ and tau PET uptake, with only 2% showing absence of both proteins. These findings will help inform the use of molecular PET in clinical treatment trials that include patients with atypical phenotypes of AD.
AB - Posterior cortical atrophy (PCA) and logopenic progressive aphasia (LPA) are clinical syndromes that commonly have underlying Alzheimer’s disease (AD), although non-AD pathologies have also been reported. PET imaging allows for identification of beta-amyloid (Aβ) and tau in AD, so we aimed to assess these in a large cohort to identify patients that do not have evidence for biomarker-defined AD. Eight-one patients, 47 PCA and 34 LPA, underwent extensive neurological and neuropsychological testing, [11C] Pittsburgh compound B, [18F] flortaucipir and [18F] fluorodeoxyglucose PETs. Global Aβ and tau-PET standardized uptake value ratios (SUVRs) were plotted for all patients and outliers, and patients with abnormally low SUVRs compared to the biomarker-classic cohort were identified. Six (7.4%) biomarker-outlier cases were identified, and three patterns were observed: (i) negative/borderline Aβ-PET and striking widespread tau-PET uptake (two LPA); (ii) negative/borderline Aβ-PET and low tau-PET uptake (three PCA) and (iii) elevated Aβ-PET uptake but mild focal tau-PET uptake (one LPA). Among the unusual patients in group ii, two patients showed no abnormal tau uptake suggesting non-AD pathology, with one developing features of cortico-basal syndrome and the other dementia with Lewy bodies. The remaining patient showed very mild focal tau uptake. This study demonstrates that a small minority (~ 8%) of PCA and LPA patients do not show the typical striking patterns of Aβ and tau PET uptake, with only 2% showing absence of both proteins. These findings will help inform the use of molecular PET in clinical treatment trials that include patients with atypical phenotypes of AD.
KW - Abnormal Aβ-PET uptake
KW - Abnormal tau-PET uptake
KW - Logopenic progressive aphasia
KW - Posterior cortical atrophy
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U2 - 10.1007/s00415-022-11330-5
DO - 10.1007/s00415-022-11330-5
M3 - Article
C2 - 36001141
AN - SCOPUS:85136952419
SN - 0340-5354
VL - 269
SP - 6613
EP - 6626
JO - Journal of Neurology
JF - Journal of Neurology
IS - 12
ER -