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Authors: Dugger, Brittany N. | Whiteside, Charisse M. | Maarouf, Chera L. | Walker, Douglas G. | Beach, Thomas G. | Sue, Lucia I. | Garcia, Angelica | Dunckley, Travis | Meechoovet, Bessie | Reiman, Eric M. | Roher, Alex E.

Article Type: Correction

DOI: 10.3233/JAD-169007

Citation: Journal of Alzheimer's Disease, vol. 54, no. 3, pp. 1249-1249, 2016

Authors: Beach, Thomas G. | Sue, Lucia I. | Walker, Douglas G. | Sabbagh, Marwan N. | Serrano, Geidy | Dugger, Brittany N. | Mariner, Monica | Yantos, Kim | Henry-Watson, Jonette | Chiarolanza, Glenn | Hidalgo, Jose A. | Souders, Leslie

Article Type: Research Article

Abstract: Amyloid imaging may revolutionize Alzheimer's disease (AD) research and clinical practice but is critically limited by an inadequate correlation between cerebral cortex amyloid plaques and dementia. Also, amyloid imaging does not indicate the extent of neurofibrillary tangle (NFT) spread throughout the brain. Currently, the presence of dementia as well as a minimal brain load of both plaques and NFTs is required for the diagnosis of AD. Autopsy studies suggest that striatal amyloid plaques may be mainly restricted to subjects in higher Braak NFT stages that meet clinicopathological diagnostic criteria for AD. Striatal plaques, which are readily identified by amyloid imaging, …might therefore be used to predict the presence of a higher Braak NFT stage and clinicopathological AD in living subjects. This study determined the sensitivity and specificity of striatal plaques for predicting a higher Braak NFT stage and clinicopathological AD in a postmortem series of 211 elderly subjects. Subjects included 87 clinicopathologically classified as non-demented elderly controls and 124 with AD. A higher striatal plaque density score (moderate or frequent) had 95.8% sensitivity, 75.7% specificity for Braak NFT stage V or VI and 85.6% sensitivity, 86.2% specificity for the presence of dementia and clinicopathological AD (National Institute on Aging – Reagan Institute “intermediate” or “high”). Amyloid imaging of the striatum may be useful as a predictor, in living subjects, of Braak NFT stage and the presence or absence of dementia and clinicopathological AD. Validation of this hypothesis will require autopsy studies of subjects that had amyloid imaging during life. Show more

Keywords: Alzheimer's disease, amyloid imaging, amyloid plaques, asymptomatic, autopsy, diagnosis, preclinical, striatum, therapy

DOI: 10.3233/JAD-2011-111340

Citation: Journal of Alzheimer's Disease, vol. 28, no. 4, pp. 869-876, 2012

Authors: Wolf, Andrew B. | Braden, B. Blair | Bimonte-Nelson, Heather | Kusne, Yael | Young, Nicole | Engler-Chiurazzi, Elizabeth | Garcia, Alexandra N. | Walker, Douglas G. | Moses, Guna S.D. | Tran, Hung | LaFerla, Frank | Lue, LihFen | Emerson Lombardo, Nancy | Valla, Jon

Article Type: Research Article

Abstract: Nutrition has been highlighted as a potential factor in Alzheimer's disease (AD) risk and decline and has been investigated as a therapeutic target. Broad-based combination diet therapies have the potential to simultaneously effect numerous protective and corrective processes, both directly (e.g., neuroprotection) and indirectly (e.g., improved vascular health). Here we administered either normal mouse chow with a broad-based nutritional supplement or mouse chow alone to aged male and female 3xTg mice and wildtype (WT) controls. After approximately 4 months of feeding, mice were given a battery of cognitive tasks and then injected with a radiolabeled glucose analog. Brains were assessed …for differences in regional glucose uptake and mitochondrial cytochrome oxidase activity, AD pathology, and inflammatory markers. Supplementation induced behavioral changes in the 3xTg, but not WT, mice, and the mode of these changes was influenced by sex. Subsequent analyses indicated that differential response to supplementation by male and female 3xTg mice highlighted brain regional strategies for the preservation of function. Several regions involved have been shown to mediate responses to steroid hormones, indicating a mechanism for sex-based vulnerability. Thus, these findings may have broad implications for the human response to future therapeutics. Show more

Keywords: Biomarkers, cytochrome-c oxidase (Complex IV), diet therapy, memory, sex, transgenic mice

DOI: 10.3233/JAD-2012-120478

Citation: Journal of Alzheimer's Disease, vol. 32, no. 1, pp. 217-232, 2012

Authors: Dugger, Brittany N. | Whiteside, Charisse M. | Maarouf, Chera L. | Walker, Douglas G. | Beach, Thomas G. | Sue, Lucia I. | Garcia, Angelica | Dunckley, Travis | Meechoovet, Bessie | Reiman, Eric M. | Roher, Alex E.

Article Type: Research Article

Abstract: Tau becomes excessively phosphorylated in Alzheimer’s disease (AD) and is widely studied within the brain. Further examination of the extent and types of tau present in peripheral tissues and their relation to AD is warranted given recent publications on pathologic spreading. Cases were selected based on the presence of pathological tau spinal cord deposits (n  = 18). Tissue samples from sigmoid colon, scalp, abdominal skin, liver, and submandibular gland were analyzed by western blot and enzyme-linked immunosorbent assays (ELISAs) for certain tau species; frontal cortex gray matter was used for comparison. ELISAs revealed brain to have the highest total tau levels, …followed by submandibular gland, sigmoid colon, liver, scalp, and abdominal skin. Western blots with antibodies recognizing tau phosphorylated at threonine 231(pT231), serine 396 and 404 (PHF-1), and an unmodified total human tau between residues 159 and 163 (HT7) revealed multiple banding patterns, some of which predominated in peripheral tissues. As submandibular gland had the highest levels of peripheral tau, a second set of submandibular gland samples were analyzed (n  = 36; 19 AD, 17 non-demented controls). ELISAs revealed significantly lower levels of pS396 (p  = 0.009) and pT231 (p  = 0.005) in AD cases but not total tau (p  = 0.18). Furthermore, pT231 levels in submandibular gland inversely correlated with Braak neurofibrillary tangle stage (p  = 0.04), after adjusting for age at death, gender, and postmortem interval. These results provide evidence that certain tau species are present in peripheral tissues. Of potential importance, submandibular gland pT231 is progressively less abundant with increasing Braak neurofibrillary tangle stage. Show more

Keywords: Braak NFT stage, colon, HT7, liver, PHF-1, propagation, skin, spread, submandibular gland, T231

DOI: 10.3233/JAD-150859

Citation: Journal of Alzheimer's Disease, vol. 51, no. 2, pp. 345-356, 2016

Authors: Dugger, Brittany N. | Serrano, Geidy E. | Sue, Lucia I. | Walker, Douglas G. | Adler, Charles H. | Shill, Holly A. | Sabbagh, Marwan N. | Caviness, John N. | Hidalgo, Jose | Saxon-LaBelle, Megan | Chiarolanza, Glenn | Mariner, Monica | Henry-Watson, Jonette | Beach, Thomas G. | The Arizona Parkinson's Disease Consortium

Article Type: Research Article

Abstract: Dementia is a frequent complication of Parkinson's disease (PD). About half of PD dementia (PDD) is hypothesized to be due to progression of the underlying Lewy body pathology into limbic regions and the cerebral cortex while the other half is thought to be due to coexistent Alzheimer's disease (AD). Clinically, however, these are indistinguishable. The spread of amyloid plaques to the striatum has been reported to be a sensitive and specific indicator of dementia due to AD. The purpose of the present study was to determine if the presence of striatal plaques might also be a useful indicator of the …presence of diagnostic levels of AD pathology within PD subjects. We analyzed neuropathologically-confirmed cases of PD without dementia (PDND, N = 31), PDD without AD (PDD, N = 31) and PD with dementia meeting clinicopathological criteria for AD (PDAD, N = 40). The minimum diagnostic criterion for AD was defined as including a clinical history of dementia, moderate or frequent CERAD cortical neuritic plaque density and Braak neurofibrillary stage III-VI. Striatal amyloid plaque densities were determined using Campbell-Switzer and Thioflavine S stains. Striatal plaque densities were significantly higher in PDAD compared to PDD (p < 0.001). The presence of striatal plaques was approximately 80% sensitive and 80% specific for predicting AD. In comparison, the presence of cerebral cortex plaques alone was highly sensitive (100%) but had poor specificity (48% to 55%). The results suggest that striatal amyloid imaging may be clinically useful for making the distinction between PDD and PDAD. Show more

Keywords: Striatum, Lewy body, diagnosis, autopsy, neuropathology, biomarker

DOI: 10.3233/JPD-2012-11073

Citation: Journal of Parkinson's Disease, vol. 2, no. 1, pp. 57-65, 2012