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- 저자 : Mony de Leon (검색결과 3 건)
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김희진,노민영,성원재,Mony de Leon,Elizabeth Pirraglia 대한고령친화산업학회 2022 대한고령친화산업학회지 Vol.14 No.2
Objective: Two core pathologies of Alzheimer's disease (AD), abnormal amyloid-beta protein deposition and increased hyper-phosphorylation of tau protein, vary according to the stage of disease. We investigated whether tau hyper-phosphorylation at serine 396 in the extra-neuronal stage of neurofibrillary tangles as an early biomarker. Methods: We studied 24 individuals with AD, 16 cognitive healthy normal controls (HC), and 19 individuals with mild cognitive impairment (MCI). We analysed cerebrospinal fluid concentrations of β-amyloid 1-40 (Aβ40), β-amyloid 1-42 (Aβ42) using sandwich ELISAs and Innotest for total tau (T-tau), phosphorylated tau 231, and phosphorylated tau 396 (P-tau 231, P-tau 396). Cerebrospinal fluid biomarkers of AD were evaluated for an association with clinical parameters and other related biological data. Results: Levels of P-tau 396 were lowest in HC compared to those in the AD and MCI groups (each p<0.001, and p=0.009). When Z-scores of total tau, P-tau 231, and P-tau 396 were compared among groups, the AD patients showed higher Z-scores of total tau and P-tau 231 than the other two groups. Differences in Z-score of P-tau 396 were observed between HC and the AD (p < 0.001) and MCI groups. The levels of Aβ42, Aβ40, T- tau, and P-tau 231 were correlated with clinical data and medial temporal atrophy in the AD and MCI groups. Conclusion: The levels of P-tau 396 in the cerebrospinal fluid showed significant differences between HC and the other two groups. Levels of P-tau 396 could be useful as a biomarker to predict disrupted neuronal integrity before the disease.
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Current Challenges for the Early Detection of Alzheimer’s Disease: Brain Imaging and CSF Studies
Rachel Mistur,Lisa Mosconi,Susan De Santi,Marla Guzman,Yi Li,Wai Tsui,Mony J. de Leon 대한신경과학회 2009 Journal of Clinical Neurology Vol.5 No.4
The development of prevention therapies for Alzheimer’s disease (AD) would greatly benefit from biomarkers that are sensitive to the subtle brain changes that occur in the preclinical stage of the disease. Reductions in the cerebral metabolic rate of glucose (CMRglc), a measure of neuronal function, have proven to be a promising tool in the early diagnosis of AD. In vivo brain 2-[ 18 F]fluoro-2-Deoxy-D-glucose-positron emission tomography (FDG-PET) imaging demonstrates consistent and progressive CMRglc reductions in AD patients, the extent and topography of which correlate with symptom severity. There is increasing evidence that hypometabolism appears during the preclinical stages of AD and can predict decline years before the onset of symptoms. This review will give an overview of FDG-PET results in individuals at risk for developing dementia, including: presymptomatic individuals carrying mutations responsible for early-onset familial AD; patients with Mild Cognitive Impairment (MCI), often a prodrome to late-onset sporadic AD; non-demented carriers of the Apolipoprotein E (ApoE) ε4 allele, a strong genetic risk factor for late-onset AD; cognitively normal subjects with a family history of AD; subjects with subjective memory complaints; and normal elderly followed longitudinally until they expressed the clinical symptoms and received post-mortem confirmation of AD. Finally, we will discuss the potential to combine different PET tracers and CSF markers of pathology to improve the early detection of AD.
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