Examining the interplay between AD pathology and intracellular/extracellular properties of cortical tissue in preclinical AD

• DOI: 10.1002/alz.075825
• Publication Date: 2023-12-25T11:19:52Z
• Authors: Hadi Hosseini; Bárbara Avelar‐Pe...; Elveda Gozdas
• Keywords: Neurite; Amyloid (mycology)

Abstract Background AD pathology affects neuronal microstructural decades before clinical manifestation of the disease. Amyloid plaques and tau tangles are key contributors to alterations in brain properties such as neurite morphology axonal transport packing, among others. It takes many years for these changes build up be reliably detected using volumetric MRI measures neurodegeneration. Here, we examined utility imaging – a biologically inspired model examining cortical microstructure examine impact amyloid on intra‐ extra‐cellular tissue further improve our mechanistic understanding development. Method We utilized multimodal data collected part ADNI‐3 including structural, multi‐shell diffusion MRI, ( 18 F‐florbetapir) F‐flortaucipir) PET. The sample included 90 cognitively normal older adults (CN:23/67 amyloid‐positive/negative, age = 72.0(8.8) years) 65 with mild cognitive impairment (MCI: 36/29 73.3(7.2) years). Neurite orientation dispersion density (NODDI) intracellular volume fraction (ICVF), index (ODI) gray matter , standardized uptake value ratio (SUVR) amyloid/tau PET thickness were extracted 360 regions defined by surface‐based HCP atlas. performed mediation analyses interplay between intracellular/extracellular also compared against detecting associated (tau burden) preclinical AD. Result Mediation showed that burden mediates (ICVF) medial lateral temporal structures (Fig.1A) whereas ODI is significant mediator effect extracellular accumulation intra‐cellular entorhinal cortex (Fig.1B) amyloid‐positive adults. Further, highest CN group, ICVF successfully distinguished from amyloid‐negative was pathology. Conclusion Overall, preliminary results suggest reduction complexity while build‐up reduces stage