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P1‐275: White Matter Neuroinflammation in Preclinical Alzheimer Disease Can Be Quantified By Diffusion Basis Spectrum Imaging
Author(s) -
Wang Qing,
Wang Yong,
Shimony Joshua S.,
Liu Jingxia,
Fagan Anne M.,
Cairns Nigel J.,
Ances Beau,
Morris John C.,
Benzinger Tammie LS.
Publication year - 2016
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 - 10.1016/j.jalz.2016.06.1025
Subject(s) - neuroinflammation , white matter , diffusion mri , imaging biomarker , fractional anisotropy , medicine , microglia , pathology , gliosis , biomarker , pathogenesis , neuroscience , psychology , disease , inflammation , magnetic resonance imaging , biology , radiology , biochemistry
(PET) ligand for imaging the paired-helical filament forms of tau deposition in the brain that are characteristic of Alzheimer’s Disease (AD). This modality of imaging together with amyloid imaging may improve understanding of the spatial pattern and magnitude of tau burden that represents a meaningful signal in the pre-dementia phases of AD. A multi-modal study is underway involving THK5351, [C-11] Pittsburgh Compound B (PiB) and advanced MRI on participants who span the disease spectrum, some of whom have up to 10 years of prior cognitive data (beginning in late middleage) with which we have established longitudinal subject-specific cognitive trajectories. Methods: As part of an ongoing study THK5351 (dynamic 90 min scan; 5.5 or 10 mCi) was administered to persons along the AD continuum from frank dementia, mild cognitive impairment, psychometric decline not sufficient for an MCI diagnosis, and stable participants recruited from the Wisconsin Registry for AD Prevention (WRAP) and Wisconsin ADRC. We also acquired [C-11]Pittsburgh compound B (PIB; 70 min dynamic acquisition; 10 mCi) and structural MRI together with historical and prospective cognitive and medical data from the source cohort study. Distribution volume ratio (DVR) maps were derived using the cerebellum as the reference region of negligible binding. After spatial normalization to standard MNI space, signal from standard regions of interest were extracted representing Braak stages I-III, IV, and V, VI and compared to global PiB burden and cognition. Results: Hippocampal adjacent MTL structures (Braak I-III) exhibited tau signal in all subjects so far (n1⁄48). Inferior and middle temporal gyri (Braak IV) exhibited moderately strong correlation with cognitive measures and global amyloid burden. Conclusions: An analogue of Braak staging for tau THK5351 signal may be useful approach for disambiguating normal aging from clinical relevant disease pathology. Just when and where tau imaging will confer a preclinical meaningful signal is the focus of this ongoing work.