Cross‐sectional and longitudinal atrophy is preferentially associated with tau rather than amyloid β positron emission tomography pathology

Abstract

Introduction Structural magnetic resonance imaging is a marker of gray matter health and decline that is sensitive to impaired cognition and Alzheimer's disease pathology. Prior work has shown that both amyloid β (Aβ) and tau biomarkers are related to cortical thinning, but it is unclear what unique influences they have on the brain. Methods Aβ pathology was measured with [ 18 F] AV-45 (florbetapir) positron emission tomography (PET) and tau was assessed with [ 18 F] AV-1451 (flortaucipir) PET in a population of 178 older adults, of which 123 had longitudinal magnetic resonance imaging assessments (average of 5.7 years) that preceded the PET acquisitions. Results In cross-sectional analyses, greater tau PET pathology was associated with thinner cortices. When examined independently in longitudinal models, both Aβ and tau were associated with greater antecedent loss of gray matter. However, when examined in a combined model, levels of tau, but not Aβ, were still highly related to change in cortical thickness. Discussion Measures of tau PET are strongly related to gray matter atrophy and likely mediate relationships between Aβ and gray matter.

Olfactory dysfunction in the pathophysiological continuum of dementia

“…The NFT burden correlates with agitation in AD patients (Tekin et al, 2001). More recently, a paper using positron emission tomography (PET) with 11C-pyridinyl-butadienyl-benzothiazole 3 (11C-PBB3) and 11C-Pittsburgh compound-B (11C-PiB), tracers for tau and Aβ respectively, indicated that elevated tau accumulation in the OFC positively correlates with OFC atrophy and apathy scale scores in the patients, while Aβ did not show any significant interaction (Gordon et al, 2018). The sparse Amyloid-β pathology in the OFC is confirmed in Tg2576 mice at 16 months (Wesson et al, 2010).…”

Spread of pathological tau proteins through communicating neurons in human Alzheimer’s disease

“…Both of these pathological phenomena can now be quantified spatially in the brains of living humans using positron emission tomography (PET), allowing for the study of disease progression before death and, indeed, before symptoms manifest [1]. β -amyloid plaques are detectable in the brain many years or even decades before dementia onset [2], but appear to have only subtle effects on cognition and brain health in humans [3, 4, 5, 6], if any. In contrast, tau neurofibrillary tangles are strongly correlated with local neurodegeneration and, in turn, cognitive impairment [7, 8].…”

Atrophy associated with tau pathology precedes overt cell death in a mouse model of progressive tauopathy

“…Recent studies in humans examined the association between tau accumulation with PET imaging tracers and cortical atrophy using structural MRI. A significant negative relationship between tracer uptake and concurrent cortical thickness was observed in the MTL (7-10), as well as in regions outside of the MTL and in neocortical areas such as the temporoparietal, posterior cingulate/precuneus, and occipital cortices (3)(4)(5)(7)(8)(9)(10)(11). In a recent longitudinal study, results…”

“…The discrepancy between tau deposits and cortical atrophy may be due to several factors. First, amyloid b (Ab) status as some studies show atrophy is preferentially associated with tau rather than Ab pathology (3)(4)(5).…”

“…Imaging techniques such as positron emission topography (PET) and magnetic resonance imaging (MRI) have been used to explore the relationship between the distribution of tau pathology and atrophy respectively, in human AD (3)(4)(5)(6)(7)(8)(9)(10)(11). However, tau PET ligands have only recently been applied in human AD and longitudinal studies are limited.…”