These mice also have a loss of TRPM5-expressing taste receptor cells in the circumvallate papillae of the tongue. While we observed no overt loss of neuron cell bodies within the primary gustatory sensory neurons, degeneration of the neurons’ peripheral axons innervating the taste bud may play a role in the observed loss of TRPM5-expressing taste receptor cells. Conclusion This data supports a potential role for peripheral taste dysfunction in AD through the selective loss of taste receptor cells. Further study is necessary to delineate the mechanisms and pathological significance of this deficit in AD.Background Dendrobium nobile is a well-known traditional Chinese herbal medicine used for age-related diseases. Dendrobium nobile Lindl alkaloid (DNLA) is the active ingredient to improve learning and memory deficits in laboratory animals. Objective The aim of the present study was to examine the anti-aging effects of long-term administration of DNLA and metformin during the aging process in senescence-accelerated mouse-prone 8 (SAMP8) mice. Methods SAMP8 mice were orally given DNLA (20 and 40 mg/kg) or metformin (80 mg/kg) starting at 6 months of age until 12 months of age. Age-matched SAMR1 mice were used as controls. DNLA and metformin treatments ameliorated behavioral deficits of 12-month-old SAMP8 mice, as determined by Rotarod, Y-maze, and Open-field tests. Results DNLA and metformin treatments prevented brain atrophy and improved morphological changes in the hippocampus and cortex, as evidenced by Nissl and H&E staining for neuron damage and loss, and by SA-β-gal staining for aging cells. DNLA and metformin treatments decreased amyloid-β1-42, AβPP, PS1, and BACE1, while increasing IDE and neprilysin for Aβ clearance. Furthermore, DNLA and metformin enhanced autophagy activity by increasing LC3-II, Beclin1, and Klotho, and by decreasing p62 in the hippocampus and cortex. Conclusion The beneficial effects of DNLA were comparable to metformin in protecting against aging-related cognitive deficits, neuron aging, damage, and loss in SAMP8 mice. The mechanisms could be attributed to increased Aβ clearance, activation of autophagy activity, and upregulation of Klotho.Background Growing evidence has shown the association between ophthalmic disorders and the risk of cognitive decline, but the conclusions were inconsistent. Objective This study aimed to verify the hypothesis that glaucoma or cataract or their combination is associated with incident dementia in Chinese older adults. Methods We followed up 1,659 non-demented community residents aged ≥60 years for an average of 5.2 years in the Shanghai Aging Study. Histories of glaucoma and cataract were collected based on self-report and medical record confirmation. Consensus diagnoses of incident dementia and Alzheimer’s disease (AD) were made based on neurological and neuropsychological assessments. Results During the follow-up, 168 cases (10.1%) of incident dementia and 124 cases (7.5%) of incident AD were identified. Participants with glaucoma at baseline had a significant risk of incident dementia (hazard ratio [HR] = 2.38, 95% confidence interval [CI] 1.08-5.23) and incident AD (HR = 2.77, 95% CI 1.17-6.56) after adjusting for confounders. There was no association between cataract and incident dementia (HR = 1.23, 95% CI 0.85-1.79) or AD (HR = 1.14, 95% CI 0.73-1.77). Those who had both glaucoma and cataract were more likely to develop dementia (HR = 3.08, 95% CI 1.29-7.37) and AD (HR = 3.72, 95% CI 1.52-9.14), compared to those without ophthalmic conditions. Conclusion Glaucoma is an independent risk factor of incident dementia and AD. The comorbidity of glaucoma and cataract may significantly increase the risk of dementia and AD.Background Dysfunction of synaptic plasticity leads to memory impairment in Alzheimer’s disease (AD). Muscone (Mus) has shown neuroprotective effects in cerebral ischemic models. However, little is known of Mus effects on AD. Objective To investigate the effects of Mus on memory functions and synaptic plasticity in 6-month-old APP/PS1 double-transgenic mice and explore the potential mechanisms. Methods Mus was intraperitoneally injected into APP/PS1 or wild-type mice, and cognitive function was assessed by Novel object recognition and Morris water maze tests. The levels of amyloid-β (Aβ) were evaluated by immunofluorescence staining and ELISA. Synaptic morphology and plasticity were evaluated by Golgi staining and long-term potentiation. Cell viability was examined by Cell Counting Kit-8 assay. The protein levels of histone deacetylase 2 (HDAC2) were accessed by western blotting and Immunofluorescence staining. The protein levels of microtubule associated protein 2 and synaptophysin were analyzed by immunofluorescence staining. The ubiquitination of HDAC2 was examined by co-immunoprecipitation. The interaction of Mus with HDAC2 was predicted by molecular docking analysis. Results Mus treatment attenuated memory dysfunction, reduced Aβ level, and enhanced synaptic plasticity in APP/PS1 mice. In addition, Mus treatment decreased the level of HDAC2 in the hippocampus of APP/PS1 mice and Aβ1-42-induced primary neurons, which might be associated with increased HDAC2 ubiquitination induced by HDAC2 and Mus interaction. Conclusion Mus protected against synaptic plasticity and memory impairment in APP/PS1 mice, and enhanced HDAC2 degradation via ubiquitination, indicating that Mus was a potential drug for AD treatment.Background/objective Hepcidin, an iron-regulating hormone, suppresses the release of iron by binding to the iron exporter protein, ferroportin, resulting in intracellular iron accumulation. Given that iron dyshomeostasis has been observed in Alzheimer’s disease (AD) together with elevated serum hepcidin levels, the current study examined whether elevated serum hepcidin levels are an early event in AD pathogenesis by measuring the hormone in cognitively normal older adults at risk of AD, based on high neocortical amyloid-β load (NAL). Methods Serum hepcidin levels in cognitively normal participants (n = 100) aged between 65-90 years were measured using ELISA. To evaluate NAL, all participants underwent 18F-florbetaben positron emission tomography. A standard uptake value ratio (SUVR) less then 1.35 was classified as low NAL (n = 65) and ≥1.35 (n = 35) was classified as high NAL. Results Serum hepcidin was significantly higher in participants with high NAL compared to those with low NAL before and after adjusting for covariates age, gender, and APOEɛ4 carriage (p less then 0.05). A receiver operating characteristic curve based on a logistic regression of the same covariates, the base model, distinguished high from low NAL (area under the curve, AUC = 0.766), but was outperformed when serum hepcidin was added to the base model (AUC = 0.794) and further improved with plasma Aβ42/40 ratio (AUC = 0.829). Conclusion The present findings indicate that serum hepcidin is increased in individuals at risk for AD and contribute to the body of evidence supporting iron dyshomeostasis as an early event of AD. Further, hepcidin may add value to a panel of markers that contribute toward identifying individuals at risk of AD; however, further validation studies are required.Background Corticobasal syndrome (CBS) is the usual clinical presentation of patients with corticobasal degeneration pathology. Nevertheless, there are CBS individuals with postmortem neuropathology typical of Alzheimer’s disease (AD). Objective In this study, we aim to detect FDG-PET metabolic signatures at the single-subject level in a CBS sample, also evaluated with cerebrospinal fluid (CSF) markers for AD pathology. Methods 21 patients (68.9±6.4 years; MMSE score = 21.7±6.3) fulfilling current criteria for CBS were enrolled. All underwent a clinical-neuropsychological assessment and an instrumental evaluation for biomarkers of neurodegeneration, amyloid and tau pathology (i.e., FDG-PET imaging and CSF Aβ42 and tau levels) at close intervals. CBS subjects were classified according to the presence or absence of CSF markers of AD pathology (i.e., low Aβ42 and high phosphorylated tau levels). Optimized voxel-based SPM procedures provided FDG-PET metabolic patterns at the single-subject and group levels. Results Eight CBS had an AD-like CSF profile (CBS-AD), while thirteen were negative (CBS-noAD). The two subgroups did not differ in demographic characteristics or global cognitive impairment. FDG-PET SPM t-maps identified different metabolic signatures. Namely, all CBS-AD patients showed the typical AD-like hypometabolic pattern involving posterior cingulate cortex, precuneus and temporo-parietal cortex, whereas CBS-noAD cases showed bilateral hypometabolism in fronto-insular cortex and basal ganglia that is typical of the frontotemporal lobar degeneration spectrum. Discussion These results strongly suggest the inclusion of FDG-PET imaging in the diagnostic algorithm of individuals with CBS clinical phenotype in order to early identify functional metabolic signatures due to different neuropathological substrates, thus improving the diagnostic accuracy.Background Neurofibrillary tangles (NFTs) and amyloid plaques are the neuropathological hallmarks in brains with Alzheimer’s disease (AD). Post-translational modifications of tau, such as phosphorylation and truncation, have been proposed as initiators in the assembly of the abnormal paired helical filaments that constitute the NFTs. Neurons and NFTs are sites of matrix metalloproteinases (MMPs). Objective The aim of this study was to analyze the relationship of MMP-9 and tau protein in brain samples with AD. Methods This study was performed on brain tissue samples from patients with early, moderate, and late AD. MMPs and tau levels were analyzed by western blot and gelatin-substrate zymography. Immunofluorescence techniques and confocal microscopy were used to analyze the presence of both proteins in NFTs. Further, molecular dynamics simulations (MDS) and protein-protein docking were conducted to predict interaction between MMP-9 and tau protein. Results MMP-9 expression was greatest in moderate and late AD, whereas MMP-2 expression was only increased in late-stage AD. Interestingly, confocal microscopy revealed NFTs in which there was co-localization of MMP-9 and tau protein. MDS and protein-protein docking predictions indicate that a high-affinity complex can be formed between MMP-9 and full-length tau protein. Conclusion These observations provide preliminary evidence of an interaction between these two proteins. Post-translational modifications of tau protein, such as C-terminal truncation or phosphorylation of amino acid residues in the MMP-9 recognition site and conformational changes in the protein, such as folding of the N-terminal sequence over the three-repeat domain, could preclude the interaction between MMP-9 and tau protein during stages of NFT development.Background Four prescription drugs (donepezil, galantamine, memantine, and rivastigmine) are approved by the US FDA to treat symptoms of Alzheimer’s disease (AD). Even modest effectiveness could potentially reduce the population-level burden of AD and related dementias (ADRD), especially for women and racial/ethnic minorities who have higher incidence of ADRD. Objective Describe the prevalence of antidementia drug use and timing of initiation relative to ADRD diagnosis among a nationally representative group of older Americans, and if there are disparities in prevalence and timing by sex and race/ethnicity. Methods Descriptive analyses and logistic regressions of Medicare claims (2008-2016) for beneficiaries who had an ADRD or dementia-related symptom diagnosis, or use of an FDA approved drug for AD. We investigate prevalence of use and timing of treatment initiation relative to ADRD diagnosis across time and beneficiary characteristics (age, sex, race/ethnicity, socioeconomic status, comorbidities). Results Among persons diagnosed with ADRD or related symptoms, 33.