Dataset Information

White matter microstructure disruption in early stage amyloid pathology.

ABSTRACT:

Introduction

Amyloid beta (Aβ) accumulation is the first pathological hallmark of Alzheimer's disease (AD), and it is associated with altered white matter (WM) microstructure. We aimed to investigate this relationship at a regional level in a cognitively unimpaired cohort.

Methods

We included 179 individuals from the European Medical Information Framework for AD (EMIF-AD) preclinAD study, who underwent diffusion magnetic resonance (MR) to determine tract-level fractional anisotropy (FA); mean, radial, and axial diffusivity (MD/RD/AxD); and dynamic [¹⁸F]flutemetamol) positron emission tomography (PET) imaging to assess amyloid burden.

Results

Regression analyses showed a non-linear relationship between regional amyloid burden and WM microstructure. Low amyloid burden was associated with increased FA and decreased MD/RD/AxD, followed by decreased FA and increased MD/RD/AxD upon higher amyloid burden. The strongest association was observed between amyloid burden in the precuneus and body of the corpus callosum (CC) FA and diffusivity (MD/RD) measures. In addition, amyloid burden in the anterior cingulate cortex strongly related to AxD and RD measures in the genu CC.

Discussion

Early amyloid deposition is associated with changes in WM microstructure. The non-linear relationship might reflect multiple stages of axonal damage.

SUBMITTER: Collij LE

PROVIDER: S-EPMC8015832 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

White matter microstructure disruption in early stage amyloid pathology.

Collij Lyduine E LE Ingala Silvia S Top Herwin H Wottschel Viktor V Stickney Kristine E KE Tomassen Jori J Konijnenberg Elles E Ten Kate Mara M Sudre Carole C Lopes Alves Isadora I Yaqub Maqsood M MM Wink Alle Meije AM Van 't Ent Dennis D Scheltens Philip P van Berckel Bart N M BNM Visser Pieter Jelle PJ Barkhof Frederik F Braber Anouk Den AD

Alzheimer's & dementia (Amsterdam, Netherlands) 20210401 1

<h4>Introduction</h4>Amyloid beta (Aβ) accumulation is the first pathological hallmark of Alzheimer's disease (AD), and it is associated with altered white matter (WM) microstructure. We aimed to investigate this relationship at a regional level in a cognitively unimpaired cohort.<h4>Methods</h4>We included 179 individuals from the European Medical Information Framework for AD (EMIF-AD) preclinAD study, who underwent diffusion magnetic resonance (MR) to determine tract-level fractional anisotrop ...[more]

PMID: 33816751

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Project description:ImportanceDown syndrome, resulting from trisomy 21, is the most prevalent chromosomal disorder and a leading cause of intellectual disability. Despite its significant impact on brain development, research on the white matter microstructure in infants with Down syndrome remains limited.ObjectiveTo investigate early white matter microstructure in infants with Down syndrome using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI).DesignInfants were recruited and scanned between March 2019 and May 2024 as participants in prospective studies conducted by the Infant Brain Imaging Study (IBIS) Network. Data were analyzed in October 2024.SettingData collection occurred at five research centers in Minnesota, Missouri, North Carolina, Pennsylvania, and Washington.ParticipantsDown syndrome and control infants were scanned at 6 months of age. Control infants had no Down syndrome diagnosis and either had a typically developing older sibling or, if they had an older sibling with autism, were confirmed not to meet clinical best estimate criteria for an autism diagnosis.ExposureDiagnosis of Down syndrome.Main outcomes and measuresThe outcome of interest was white matter microstructure quantified using DTI and NODDI measures.ResultsA total of 49 Down syndrome (28 [57.14%] female) and 37 control (18 [48.65%] female) infants were included. Infants with Down syndrome showed significant reductions in fractional anisotropy and neurite density index across multiple association tracts, particularly in the inferior fronto-occipital fasciculus and superior longitudinal fasciculus II, consistent with reduced structural integrity and neurite density. These tracts also demonstrated increased radial diffusivity, suggesting delayed myelination. The inferior fronto-occipital fasciculus and uncinate fasciculus exhibited increased neurite dispersion and fanning in Down syndrome infants, reflected by elevated orientation dispersion index. Notably, the optic tracts in Down syndrome infants exhibited a distinct pattern of elevated fractional anisotropy and axial diffusivity, and lower radial diffusivity and orientation dispersion index, suggesting an early maturation of these pathways.Conclusions and relevanceThis first characterization of white matter microstructure in Down syndrome infants reveals widespread white matter developmental delays. These findings provide new insights into the early neurodevelopment of Down syndrome and may inform early therapeutic interventions.

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Dataset Information

White matter microstructure disruption in early stage amyloid pathology.

Introduction

Methods

Results

Discussion

Publications

White matter microstructure disruption in early stage amyloid pathology.

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