Pre-Clinical Detection of Alzheimer's Disease Using FDG-PET, with or without Amyloid Imaging
Authors: Mosconi, Lisa | Berti, Valentina | Glodzik, Lidia | Pupi, Alberto | De Santi, Susan | de Leon, Mony J.
Article Type: Review Article
Abstract: The development of prevention therapies for Alzheimer's disease (AD) would greatly benefit from biomarkers that are sensitive to subtle brain changes occurring in the preclinical stage of the disease. Early diagnostics is necessary to identify and treat at risk individuals before irreversible neuronal loss occurs. In vivo imaging has long been used to evaluate brain structural and functional abnormalities as predictors of future AD in non-demented persons. Prior to development of amyloid-β (Aβ) tracers for positron emission tomography (PET), the most widely utilized PET tracer in AD was 2-[18F]fluoro-2-Deoxy-D-glucose (FDG) PET. For over 20 years, FDG-PET has been used to …measure cerebral metabolic rates of glucose (CMRglc), a proxy for neuronal activity, in AD. Many studies have shown that CMRglc reductions occur early in AD, correlate with disease progression, and predict histopathological diagnosis. This paper reviews reports of clinical and preclinical CMRglc reductions observed in association with genetic and non-genetic risk factors for AD. We then briefly review brain Aβ PET imaging studies in AD and discuss the potential of combining symptoms-sensitive FDG-PET measures with pathology-specific Aβ-PET to improve the early detection of AD. Show more
Keywords: Amyloid-β, cerebral metabolic rate of glucose (CMRglc), normal aging, positron emission tomography, preclinical detection
DOI: 10.3233/JAD-2010-091504
Citation: Journal of Alzheimer's Disease, vol. 20, no. 3, pp. 843-854, 2010
Effects of Memantine on Cerebrospinal Fluid Biomarkers of Neurofibrillary Pathology
Authors: Glodzik, Lidia | De Santi, Susan | Rich, Kenneth E. | Brys, Miroslaw | Pirraglia, Elizabeth | Mistur, Rachel | Switalski, Remigiusz | Mosconi, Lisa | Sadowski, Martin | Zetterberg, Henrik | Blennow, Kaj | de Leon, Mony J.
Article Type: Short Communication
Abstract: Previous studies showed that memantine inhibits tau hyperphosphorylation in vitro. In this study, phosphorylated tau (P-tau) and total tau (T-tau) were measured before and after 6 month treatment with memantine in 12 subjects ranging from normal cognition with subjective memory complaints, through mild cognitive impairment to mild Alzheimer's disease. Thirteen non-treated individuals served as controls. Treatment was associated with a reduction of P-tau in subjects with normal cognition. No treatment effects were seen among impaired individuals, suggesting that longer treatment time may be necessary to achieve biomarker effect in this group.
Keywords: Alzheimer's disease, biomarkers, cerebrospinal fluid, memantine, phosphorylated tau, total tau
DOI: 10.3233/JAD-2009-1183
Citation: Journal of Alzheimer's Disease, vol. 18, no. 3, pp. 509-513, 2009
Shift from fibrillar to nonfibrillar Aß deposits in the neocortex of subjects with Alzheimer disease
Authors: Wegiel, Jerzy | Bobinski, Maciej | Tarnawski, Michal | Dziewiatkowski, Jerzy | Popovitch, Eirene | Bobinski, Margaret | Lach, Boleslaw | Reisberg, Barry | Miller, Douglas C. | de Santi, Susan | de Leon, Mony J.
Article Type: Research Article
Abstract: A morphometric study of amyloid-ß-positive plaques in the neocortex of eight non-demented people from 68 to 82 years of age and 17 subjects with late-stage Alzheimer disease (GDS stage 7/FAST stages 7a–f) from 73 to 93 years of age shows a shift from prevalence of fibrillar plaques to prevalence of nonfibrillar plaques. In the aged, non-demented subjects, about 4/mm2 plaques are detectable in the neocortex, and the majority are fibrillar plaques. Specifically, 64% found to be classical fibrillar and Thioflavin-S-positive bright primitive plaques. A lower percentage of pale primitive plaques (35%) relatively small proportion of plaques that are poor in …thioflavin S-positive fibrils. The numerical density of plaques in the severe stage of AD increases to about 41/mm2 . Severely demented subjects appear to maintain an active process of fibrillar plaque formation. This is reflected in the presence of 3% bright primitive plaques. Severely demented subjects also manifest plaque degradation, reflected in the presence of 22% and 48% percentages of classical fibrillar plaques in non-demented subjects and in the end stage of disease suggest that once activated, the process of fibrillar plaque formation persists at a somewhat stable rate during the whole course of brain amyloidosis. Show more
Keywords: Alzheimer disease, diffuse plaques, fibrillar plaques, morphometry
DOI: 10.3233/JAD-2001-3108
Citation: Journal of Alzheimer's Disease, vol. 3, no. 1, pp. 49-57, 2001
Magnetic Resonance Imaging Improves Cerebrospinal Fluid Biomarkers in the Early Detection of Alzheimer's Disease
Authors: Brys, Miroslaw | Glodzik, Lidia | Mosconi, Lisa | Switalski, Remigiusz | De Santi, Susan | Pirraglia, Elizabeth | Rich, Kenneth | Kim, Byeong C. | Mehta, Pankaj | Zinkowski, Ray | Pratico, Domenico | Wallin, Anders | Zetterberg, Henrik | Tsui, Wai H. | Rusinek, Henry | Blennow, Kaj | de Leon, Mony J.
Article Type: Research Article
Abstract: Little is known of combined utility of magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) biomarkers for prediction of Alzheimer's disease (AD) and longitudinal data is scarce. We examined these biomarkers at baseline and longitudinally in incipient AD. Forty-five subjects [21 controls (NL-NL), 16 stable MCI (MCI-MCI), 8 MCI who declined to AD (MCI-AD)] received MRI and lumbar puncture at baseline and after 2 years. CSF measures included total and phosphorylated tau (T-tau, P-tau231 ), amyloid-β (Aβ42 /Aβ40 ) and isoprostane. Voxel-based morphometry identified gray matter concentration (GMC) differences best distinguishing study groups and individual GMC values were calculated. Rate …of medial temporal lobe (MTL) atrophy was examined using regional boundary shift (rBS) method. At baseline, for MRI, MCI-AD showed reduced GMC-MTL, and for CSF higher CSF T-tau, P-tau231 , IP and lower Aβ42 /Aβ40 as compared with MCI-MCI or NL-NL. Longitudinally, rBS-MTL atrophy was higher in MCI-AD than in either MCI-MCI or NL-NL, particularly in the left hemisphere. CSF data showed longitudinally greater increases of isoprostane in MCI-AD as compared with NL-NL. Combining baseline CSF-P-tau231 and GMC-MTL significantly increased overall prediction of AD from 74% to 84% (pstep < 0.05). These results provide support for including multiple modalities of biomarkers in the identification of memory clinic patients at increased risk for dementia. Show more
Keywords: Alzheimer's disease, brain atrophy, cerebrospinal fluid biomarkers, early diagnosis
DOI: 10.3233/JAD-2009-0968
Citation: Journal of Alzheimer's Disease, vol. 16, no. 2, pp. 351-362, 2009