Dataset Information

Tau-PET uptake: Regional variation in average SUVR and impact of amyloid deposition.

ABSTRACT:

Introduction

Tau-positron emission tomography (PET) imaging with AV1451 is sensitive to Alzheimer disease (AD)-related tau deposition in the brain. We (1) examined regional variation of average tau-PET standardized uptake value ratios (SUVRs) in a young normal population (30-49 years) and corrected for the regional variability and (2) tested if the standardized values (z-scores) scaled appropriately to capture regional Alzheimer-specific (i.e., amyloid sensitive) tau-PET changes in individuals aged 50+ years.

Methods

We identified 490 individuals (70 between 30-49 years as a reference group and 420 cognitively normal between 50-95 years of age) with tau-PET and amyloid PET scans from the Mayo Clinic Study of Aging.

Results

There was intrinsic regional variability in average tau-PET SUVR with uptakes higher in some regions than others, even in the younger individuals who would have minimal or no neurofibrillary tangles. We corrected for this using region of interest-specific z-scores based on the reference group. Amyloid and tau-PET uptake were associated throughout the brain after adjusting for age, with the highest correlations in the medial temporal regions.

Discussion

Regions with high-average SUVR are not necessarily those with the greatest tau pathology. Standardization is therefore recommended. Standardization of the data "realigns" the data such that the regional tau z-scores are informative of the disease process, that is, regions with high z-scores now coincide with regions correlated with amyloid deposition. Medial temporal structures, specifically entorhinal cortex-tau, may be useful as an AD-specific tau-PET signature due to its sensitivity to amyloid.

SUBMITTER: Vemuri P

PROVIDER: S-EPMC5257031 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Tau-PET uptake: Regional variation in average SUVR and impact of amyloid deposition.

Vemuri Prashanthi P Lowe Val J VJ Knopman David S DS Senjem Matthew L ML Kemp Bradley J BJ Schwarz Christopher G CG Przybelski Scott A SA Machulda Mary M MM Petersen Ronald C RC Jack Clifford R CR

Alzheimer's & dementia (Amsterdam, Netherlands) 20161221

<h4>Introduction</h4>Tau-positron emission tomography (PET) imaging with AV1451 is sensitive to Alzheimer disease (AD)-related tau deposition in the brain. We (1) examined regional variation of average tau-PET standardized uptake value ratios (SUVRs) in a young normal population (30-49 years) and corrected for the regional variability and (2) tested if the standardized values (z-scores) scaled appropriately to capture regional Alzheimer-specific (i.e., amyloid sensitive) tau-PET changes in indiv ...[more]

PMID: 28138510

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Project description:INTRODUCTION:Tau pathology is a major age-related event in Down syndrome with Alzheimer's disease (DS-AD). Although recently, several different Tau PET tracers have been developed as biomarkers for AD, these tracers showed different binding properties in Alzheimer disease and other non-AD tauopathies. They have not been yet investigated in tissue obtained postmortem for DS-AD cases. Here, we evaluated the binding characteristics of two Tau PET tracers (3H-MK6240 and 3H-THK5117) and one amyloid (3H-PIB) ligand in the medial frontal gyrus (MFG) and hippocampus (HIPP) in tissue from adults with DS-AD and DS cases with mild cognitive impairment (MCI) compared to sporadic AD. METHODS:Tau and amyloid autoradiography were performed on paraffin-embedded sections. To confirm respective ligand targets, adjacent sections were immunoreacted for phospho-Tau (AT8) and stained for amyloid staining using Amylo-Glo. RESULTS:The two Tau tracers showed a significant correlation with each other and with AT8, suggesting that both tracers were binding to Tau deposits. 3H-MK6240 Tau binding correlated with AT8 immunostaining but to a lesser degree than the 3H-THK5117 tracer, suggesting differences in binding sites between the two Tau tracers. 3H-THK5117, 3H-MK6240 and 3H-PIB displayed dense laminar binding in the HIPP and MFG in adult DS brains. A regional difference in Tau binding between adult DS and AD was observed suggesting differential regional Tau deposition in adult DS compared to AD, with higher THK binding density in the MFG in adult with DS compared to AD. No significant correlation was found between 3H-PIB and Amylo-Glo staining in adult DS brains suggesting that the amyloid PIB tracer binds to additional sites. CONCLUSIONS:This study provides new insights into the regional binding distribution of a first-generation and a second-generation Tau tracer in limbic and neocortical regions in adults with DS, as well as regional differences in Tau binding in adult with DS vs. those with AD. These findings provide new information about the binding properties of two Tau radiotracers for the detection of Tau pathology in adults with DS in vivo and provide valuable data regarding Tau vs. amyloid binding in adult DS compared to AD.

Project description:BACKGROUND:The aim of this longitudinal study was to assess with positron emission tomography (PET) the relationship between levels of inflammation and the loads of aggregated ?-amyloid and tau at baseline and again after 2 years in prodromal Alzheimer's disease. METHODS:Forty-three subjects with mild cognitive impairment (MCI) had serial 11C-PK11195 PET over 2 years to measure inflammation changes, and 11C-PiB PET to determine ?-amyloid fibril load; 22 also had serial 18F-Flortaucipir PET to determine tau tangle load. Cortical surface statistical mapping was used to localise areas showing significant changes in tracer binding over time and to interrogate correlations between tracer binding of the tracers at baseline and after 2 years. RESULTS:Those MCI subjects with high 11C-PiB uptake at baseline (classified as prodromal Alzheimer's disease) had raised inflammation levels which significantly declined across cortical regions over 2 years although their ?-amyloid levels continued to rise. Those MCI cases who had low/normal 11C-PiB uptake at baseline but their levels then rose over 2 years were classified as prodromal AD with low Thal phase 1-2 amyloid deposition at baseline. They showed levels of cortical inflammation which correlated with their rising ?-amyloid load. Those MCI cases with baseline low 11C-PiB uptake that remained stable were classified as non-AD, and they showed no correlated inflammation levels. Finally, MCI cases which showed both high 11C-PiB and 18F-Flortaucipir uptake at baseline (MCI due to AD) showed a further rise in their tau tangle load over 2 years with a correlated rise in levels of inflammation. CONCLUSIONS:Our baseline and 2-year imaging findings are compatible with a biphasic trajectory of inflammation in Alzheimer's disease: MCI cases with low baseline but subsequently rising ?-amyloid load show correlated levels of microglial activation which then later decline when the ?-amyloid load approaches AD levels. Later, as tau tangles form in ?-amyloid positive MCI cases with prodromal AD, the rising tau load is associated with higher levels of inflammation.

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Project description:BackgroundInsulin resistance (IR) and type 2 diabetes have been found to increase the risk for Alzheimer's clinical syndrome in epidemiologic studies but have not been associated with tau tangles in neuropathological research and have been inconsistently associated with cerebrospinal fluid P-tau181. IR and type 2 diabetes are well-recognized vascular risk factors. Some studies suggest that cardiovascular risk may act synergistically with cortical amyloid to increase tau measured using tau PET. Utilizing data from largely nondemented middle-aged and older adult cohorts enriched for AD risk, we investigated the association of IR and diabetes to tau PET and whether amyloid moderated those relationships.MethodsParticipants were enrolled in either the Wisconsin Registry for Alzheimer's Prevention (WRAP) or Wisconsin Alzheimer's Disease Research Center (WI-ADRC) Clinical Core. Two partially overlapping samples were studied: a sample characterized using HOMA-IR (n=280 WRAP participants) and a sample characterized on diabetic status (n=285 WRAP and n=109 WI-ADRC). IR was measured using the homeostasis model assessment of insulin resistance (HOMA-IR). Tau PET employing the radioligand 18F-MK-6240 was used to detect AD-specific aggregated tau. Linear regression tested the relationship of IR and diabetic status to tau PET standardized uptake value ratio (SUVR) within the entorhinal cortex and whether relationships were moderated by amyloid assessed by amyloid PET distribution volume ratio (DVR) and amyloid PET positivity status.ResultsNeither HOMA-IR nor diabetic status was significantly associated with tau PET SUVR. The relationship between IR and tau PET SUVR was not moderated by amyloid PET DVR or positivity status. The association between diabetic status and tau PET SUVR was not significantly moderated by amyloid PET DVR but was significantly moderated by amyloid PET positivity status. Among the amyloid PET-positive participants, the estimated marginal tau PET SUVR mean was higher in the diabetic (n=6) relative to the nondiabetic group (n=88).ConclusionFindings indicate that IR may not be related to tau in generally healthy middle-aged and older adults who are in the early stages of the AD clinicopathologic continuum but suggest the need for additional research to investigate whether a synergistic relationship between type 2 diabetes and amyloid is associated with increased tau levels.

Dataset Information

Tau-PET uptake: Regional variation in average SUVR and impact of amyloid deposition.

Introduction

Methods

Results

Discussion

Publications

Tau-PET uptake: Regional variation in average SUVR and impact of amyloid deposition.

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