Dataset Information

Defining imaging biomarker cut points for brain aging and Alzheimer's disease.

ABSTRACT:

Introduction

Our goal was to develop cut points for amyloid positron emission tomography (PET), tau PET, flouro-deoxyglucose (FDG) PET, and MRI cortical thickness.

Methods

We examined five methods for determining cut points.

Results

The reliable worsening method produced a cut point only for amyloid PET. The specificity, sensitivity, and accuracy of cognitively impaired versus young clinically normal (CN) methods labeled the most people abnormal and all gave similar cut points for tau PET, FDG PET, and cortical thickness. Cut points defined using the accuracy of cognitively impaired versus age-matched CN method labeled fewer people abnormal.

Discussion

In the future, we will use a single cut point for amyloid PET (standardized uptake value ratio, 1.42; centiloid, 19) based on the reliable worsening cut point method. We will base lenient cut points for tau PET, FDG PET, and cortical thickness on the accuracy of cognitively impaired versus young CN method and base conservative cut points on the accuracy of cognitively impaired versus age-matched CN method.

SUBMITTER: Jack CR

PROVIDER: S-EPMC5344738 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Publications

Defining imaging biomarker cut points for brain aging and Alzheimer's disease.

Jack Clifford R CR Wiste Heather J HJ Weigand Stephen D SD Therneau Terry M TM Lowe Val J VJ Knopman David S DS Gunter Jeffrey L JL Senjem Matthew L ML Jones David T DT Kantarci Kejal K Machulda Mary M MM Mielke Michelle M MM Roberts Rosebud O RO Vemuri Prashanthi P Reyes Denise A DA Petersen Ronald C RC

Alzheimer's & dementia : the journal of the Alzheimer's Association 20160930 3

<h4>Introduction</h4>Our goal was to develop cut points for amyloid positron emission tomography (PET), tau PET, flouro-deoxyglucose (FDG) PET, and MRI cortical thickness.<h4>Methods</h4>We examined five methods for determining cut points.<h4>Results</h4>The reliable worsening method produced a cut point only for amyloid PET. The specificity, sensitivity, and accuracy of cognitively impaired versus young clinically normal (CN) methods labeled the most people abnormal and all gave similar cut poi ...[more]

PMID: 27697430

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Project description:BackgroundDiscovery of early-stage biomarkers is a long-sought goal of Alzheimer's disease (AD) diagnosis. Age is the greatest risk factor for most AD and accumulating evidence suggests that age-dependent elevation of asparaginyl endopeptidase (AEP) in the brain may represent a new biological marker for predicting AD. However, this speculation remains to be explored with an appropriate assay method because mammalian AEP exists in many organs and the level of AEP in body fluid isn't proportional to its concentration in brain parenchyma. To this end, we here modified gold nanoparticle (AuNPs) into an AEP-responsive imaging probe and choose transgenic APPswe/PS1dE9 (APP/PS1) mice as an animal model of AD. Our aim is to determine whether imaging of brain AEP can be used to predict AD pathology.ResultsThis AEP-responsive imaging probe AuNPs-Cy5.5-A&C consisted of two particles, AuNPs-Cy5.5-AK and AuNPs-Cy5.5-CABT, which were respectively modified with Ala-Ala-Asn-Cys-Lys (AK) and 2-cyano-6-aminobenzothiazole (CABT). We showed that AuNPs-Cy5.5-A&C could be selectively activated by AEP to aggregate and emit strong fluorescence. Moreover, AuNPs-Cy5.5-A&C displayed a general applicability in various cell lines and its florescence intensity correlated well with AEP activity in these cells. In the brain of APP/PS1 transgenic mice , AEP activity was increased at an early disease stage of AD that precedes formation of senile plaques and cognitive impairment. Pharmacological inhibition of AEP with δ-secretase inhibitor 11 (10 mg kg-1, p.o.) reduced production of β-amyloid (Aβ) and ameliorated memory loss. Therefore, elevation of AEP is an early sign of AD onset. Finally, we showed that live animal imaging with this AEP-responsive probe could monitor the up-regulated AEP in the brain of APP/PS1 mice.ConclusionsThe current work provided a proof of concept that assessment of brain AEP activity by in vivo imaging assay is a potential biomarker for early diagnosis of AD.

Dataset Information

Defining imaging biomarker cut points for brain aging and Alzheimer's disease.

Introduction

Methods

Results

Discussion

Publications

Defining imaging biomarker cut points for brain aging and Alzheimer's disease.

Similar Datasets

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