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Myelin abnormalities as the earliest symptoms of dementia – harmonizing neuroimaging and cell biology

Description: Objectives The causes of age-related dementias, including Alzheimer's disease (AD), remain largely unknown. Substantial neuroimaging evidences suggest that loss of myelin integrity is a strong correlate of cognitive decline in the elderly and may play a causative part in the etiology of dementia. This project aims to correlate neuroimaging and histopathology to understand the cell biology underlying these clinical findings. Hypothesis to be tested MRI-detectable myelin abnormalities in ageing and dementia individuals are caused, and probably initiated, by cellular pathology of the oligodendrocytes of the brain. Design and subjects Three cohorts of archrival MRI data of AD(n=19), multiple sclerosis(n=17) and neuropsychiatric systemic lupus erythematosus(n=40) and their age matching controls (n=58) will be analyzed. AD mice models(R.140, ApoE3 and ApoE4) and their controls(n=8/group), will be studied longitudinally with MRI. Study instruments Human MRI and MRI-spectroscopy(MRS) datasets will be meta-analyzed for age-dependent demyelination and MRS signature at the demyelinating site. Similar MRI-detectable myelin change will be studied in mice model of different ages. The behavior, histopathological, gene expression and biochemical change at the myelin abnormalities site will be correlated with MRI findings. Main outcome measures The longitudinal changes in MRI-detected myelin abnormalities will be correlated with the cellular change of oligodendrocyte lineage. Data analysis and expected results Correlation between MRI and histopathology will be tested by Pearson correlation and one-way ANVOA among groups. Potential application The results will elucidate the cellular pathology underlying findings of MRI-detectable myelin change in dementia patients and ask if demyelination is an early diagnostic marker for dementia.

Funder: Health and Medical Research Fund

Amount: HKD 1,200,000

Funding type: grant

Funder scheme: HMRF - Advanced Medical Research

Start date: 2016-01-01

Investigator: Karl HERRUP

Institution: Division of Life Science, The Hong Kong University of Science and Technology

Funded outputs count: 0

Funder award ID: 05163736

OpenAlex ID: G7613610883