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Clinical and neurodegenerative features associated with amyloid‐β‐negative medial temporal tau deposition as measured by multimodal PET imaging
Author(s) -
Grothe Michel J.,
Moscoso Alexis,
Schöll Michael
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.040033
Subject(s) - tauopathy , temporal lobe , standardized uptake value , neuroimaging , pathology , entorhinal cortex , dementia , psychology , medicine , tau pathology , neuroscience , positron emission tomography , alzheimer's disease , disease , neurodegeneration , hippocampus , epilepsy
Background The combined accumulation of amyloid‐beta (Aβ) plaques and tau neurofibrillary tangles is the defining feature for Alzheimer’s disease (AD) pathology. However, tau can also accumulate in the medial temporal lobe in the absence of Aβ pathology, a neuropathological condition termed primary age‐related tauopathy (PART) that can result in amnestic impairments similar to early stage AD. Here we aimed to describe clinical and neurodegenerative characteristics of older amnestic individuals with Aβ‐negative medial temporal tau deposition as revealed by in‐vivo PET imaging. Method In the ADNI cohort we identified a total of 174 older individuals with amnestic deficits (155 amnestic mild cognitive impairment (aMCI), 19 mild AD‐type dementia (ADD)), who had tau‐sensitive ([18F]flortaucipir) and Aβ‐sensitive ([18F]florbetapir or [18F]florbetaben) PET acquisitions, as well as structural MRI and [18F]FDG‐PET scans. Presence/absence of Aβ and tau pathology was determined by applying sensitive cutoffs to Aβ‐PET‐derived centiloid values (>12 centiloids) and entorhinal flortaucipir SUVR (inferior cerebellum reference; >1.175 SUVR, corresponding to the highest value observed in Aβ‐negative healthy controls below 65y (N=13, 56‐63y)). Clinical, genetic, and neuroimaging data of patients with Aβ‐negative tau deposition (A‐/T+, N=19, 17/2 aMCI/ADD) was contrasted to A+/T+ (N=81, 65/16 aMCI/ADD) and A‐/T‐ patients (N=38, 37/1 aMCI/ADD) as well as to A‐/T‐ healthy controls (N=40). Result A‐/T+ patients had a markedly lower proportion of APOE‐ε4 carriers (16%) compared to A+/T+ (69%, p<0.001), and a higher proportion of APOE‐ε2 carriers (42%) compared to A+/T+ (1%, p<0.001) and A‐/T‐ (15%, p=0.04). A‐/T+ patients had comparable memory and executive deficits compared to A‐/T‐, but were less impaired than A+/T+, even when excluding ADD patients. In brain‐wide neuroimaging analyses, tau deposition in A‐/T+ was mainly restricted to the medial/inferior temporal lobe and related limbic structures (Fig‐1). These areas also showed marked hypometabolism, but only subtle gray matter atrophy. By contrast, A+/T+ patients showed a widespread neocortical tau distribution, as well as marked neurodegeneration on both FDG‐PET and structural MRI. A‐/T‐ patients did not show significant neuroimaging abnormalities. Conclusion Aβ‐negative tau deposition as evidenced by PET associates with distinct clinical, genetic, and neurodegenerative features that resemble that of neuropathologically‐defined PART and may allow to study this condition in‐vivo .