Browsing by Author "Hirschfeld, Lauren Rose"

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    Myelin repair in Alzheimer's disease: a review of biological pathways and potential therapeutics
    (BMC, 2022-10-26) Hirschfeld, Lauren Rose; Risacher, Shannon L.; Nho, Kwangsik; Saykin, Andrew J.; Radiology and Imaging Sciences, School of Medicine
    This literature review investigates the significant overlap between myelin-repair signaling pathways and pathways known to contribute to hallmark pathologies of Alzheimer's disease (AD). We discuss previously investigated therapeutic targets of amyloid, tau, and ApoE, as well as other potential therapeutic targets that have been empirically shown to contribute to both remyelination and progression of AD. Current evidence shows that there are multiple AD-relevant pathways which overlap significantly with remyelination and myelin repair through the encouragement of oligodendrocyte proliferation, maturation, and myelin production. There is a present need for a single, cohesive model of myelin homeostasis in AD. While determining a causative pathway is beyond the scope of this review, it may be possible to investigate the pathological overlap of myelin repair and AD through therapeutic approaches.
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    Myelin repair in Alzheimer's disease: a review of biological pathways and potential therapeutics
    (Springer, 2022-10-26) Hirschfeld, Lauren Rose; Risacher, Shannon L.; Nho, Kwangsik; Saykin, Andrew J.; Radiology and Imaging Sciences, School of Medicine
    This literature review investigates the significant overlap between myelin-repair signaling pathways and pathways known to contribute to hallmark pathologies of Alzheimer's disease (AD). We discuss previously investigated therapeutic targets of amyloid, tau, and ApoE, as well as other potential therapeutic targets that have been empirically shown to contribute to both remyelination and progression of AD. Current evidence shows that there are multiple AD-relevant pathways which overlap significantly with remyelination and myelin repair through the encouragement of oligodendrocyte proliferation, maturation, and myelin production. There is a present need for a single, cohesive model of myelin homeostasis in AD. While determining a causative pathway is beyond the scope of this review, it may be possible to investigate the pathological overlap of myelin repair and AD through therapeutic approaches.
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    White matter integrity is associated with cognition and amyloid burden in older adult Koreans along the Alzheimer's disease continuum
    (medRxiv, 2023-04-06) Hirschfeld, Lauren Rose; Deardorff, Rachael; Chumin, Evgeny J.; Wu, Yu-Chien; McDonald, Brenna C.; Cao, Sha; Risacher, Shannon L.; Yi, Dahyun; Byun, Min Soo; Lee, Jun-Young; Kim, Yu Kyeong; Kang, Koung Mi; Sohn, Chul-Ho; Nho, Kwangsik; Saykin, Andrew J.; Lee, Dong Young; KBASE Research Group; Radiology and Imaging Sciences, School of Medicine
    Background: White matter (WM) microstructural changes in the hippocampal cingulum bundle (CBH) in Alzheimer's disease (AD) have been described in cohorts of largely European ancestry but are lacking in other populations. Methods: We assessed the relationship between CBH WM integrity and cognition or amyloid burden in 505 Korean older adults aged ≥55 years, including 276 cognitively normal older adults (CN), 142 mild cognitive impairment (MCI), and 87 AD, recruited as part of the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's disease (KBASE) at Seoul National University. Results: Compared to CN, AD and MCI subjects showed decreased WM integrity in the bilateral CBH. Cognition, mood, and higher amyloid burden were also associated with poorer WM integrity in the CBH. Conclusion: These findings are consistent with patterns of WM microstructural damage previously reported in non-Hispanic White (NHW) MCI/AD cohorts, reinforcing existing evidence from predominantly NHW cohort studies.
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    White Matter Microstructural Changes in the Cingulum Bundle of the Hippocampus in Alzheimer's Disease
    (2023-07) Hirschfeld, Lauren Rose; Risacher, Shannon L.; Saykin, Andrew J.; Block, Michelle L.; Wu, Yu-Chien; Nho, Kwangsik; Cao, Sha
    Alzheimer’s disease (AD), the most common dementia, is the seventh leading cause of death for adults in the US. Recent FDA-approved therapeutics targeting hallmark amyloid pathology may slow but do not yet halt the disease. Thus, it is likely that other factors, such as neurodegeneration, play a role in disease development. Compromised white matter (WM) microstructural integrity may be a promising biomarker for disease progression, as it has been demonstrated in both preclinical and clinical AD. WM microstructural changes can be estimated using diffusion tensor imaging (DTI), a noninvasive imaging modality which measures the diffusion of water molecules within brain tissue. First, literature describing a biological relationship between signaling pathways involved in both insufficient myelin-repair mechanisms and AD pathology was assessed to establish a foundation for studying WM in the context of AD. Then, DTI was used to assess possible WM microstructural changes of the cingulum bundle of the hippocampus (CBH), a disease-relevant region, in the KBASE cohort of older Korean adults on the AD continuum. Similar to White cohorts of European ancestry, DTI values corresponding to worsening WM microstructure occurred in a stepwise fashion across diagnostic stages and were associated with both cognition and amyloid deposition. In a sample of older adults from the Indiana Memory and Aging Study (IMAS), CBH microstructure was a sensitive biomarker of preclinical conversion from cognitively unimpaired status to mild cognitive impairment. Finally, a novel extension of the T1/T2 weighted ratio imaging method, thought to estimate myelin- related tissue integrity, yielded values in IMAS subjects reflective of previously observed DTI patterns. The complex interplay between amyloid, tau, and neurodegeneration in AD is not yet fully characterized. This research shows decreased integrity of WM microstructure in the CBH, which may be useful as a biomarker of early disease conversion to MCI.