Alzheimer’s disease and senile dementia: loss of neurons in the basal forebrain

Author: Whitehouse, P.J.; Price, D.L.; Struble, R.G.; Clark, A.W.; Coyle, J.T.; Delon, M.R. Description: Recent evidence indicates that the nucleus basalis of Meynert, a distinct population of basal forebrain neurons, is a major source of cholinergic innervation of the cerebral cortex. Postmortem studies have previously demonstrated profound reduction in the presynaptic markers for cholinergic neurons in the cortex of patients with Alzheimer’s disease and senile dementia of the Alzheimer’s type. The results of this study show that neurons of the nucleus basalis of Meynert undergo a profound (greater than 75…

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Alzheimer’s disease: treatments in discovery and development

Author: Citron, M. Description: Alzheimer’s disease is the single biggest unmet medical need in neurology. Current drugs are safe, but of limited benefit to most patients. This review discusses the scientific basis and current status of promising disease-modifying therapies in the discovery and development stages. I describe the major targets of anti-amyloid therapy and the main focus of disease modification approaches. In addition, two new potential treatment approaches supported by retrospective epidemiology are outlined. Subject headings: Alzheimer Disease/metabolism/physiopathology/therapy; Amyloid beta-Peptides/antagonists & inhibitors/biosynthesis; Animals; Brain/drug effects/metabolism/physiopathology; Disease Models, Animal; Drug Design;…

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CXCR6 orchestrates brain CD8+ T cell residency and limits mouse Alzheimer’s disease pathology

Author: Su, Wei; Saravia, Jordy; Risch, Isabel; Rankin, Sherri; Guy, Cliff; Chapman, Nicole M.; Shi, Hao; Sun, Yu; Kc, Anil; Li, Wei; Huang, Hongling; Lim, Seon Ah; Hu, Haoran; Wang, Yan; Liu, Danting; Jiao, Yun; Chen, Ping-Chung; Soliman, Hadeer; Yan, Koon-Kiu; Zhang, Jonathan; Vogel, Peter; Liu, Xueyan; Serrano, Geidy E.; Beach, Thomas G.; Yu, Jiyang; Peng, Junmin; Chi, Hongbo Description: Neurodegenerative diseases, including Alzheimer’s disease (AD), are characterized by innate immune-mediated inflammation, but functional and mechanistic effects of the adaptive immune system remain unclear. Here we identify brain-resident CD8+ T…

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Chronic stress as a risk factor for Alzheimer’s disease

Author: Machado, A.; Herrera, A.J.; de Pablos, R.M.; Espinosa-Oliva, A.M.; Sarmiento, M.; Ayala, A.; Venero, J.L.; Santiago, M.; Villaran, R.F.; Delgado-Cortes, M.J.; Arguelles, S.; Cano, J. Description: This review aims to point out that chronic stress is able to accelerate the appearance of Alzheimer’s disease (AD), proposing the former as a risk factor for the latter. Firstly, in the introduction we describe some human epidemiological studies pointing out the possibility that chronic stress could increase the incidence, or the rate of appearance of AD. Afterwards, we try to justify these…

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Diagnostic Biomarkers of Alzheimer’s Disease as Identified in Saliva using 1H NMR-Based Metabolomics

Author: Yilmaz, Ali; Geddes, Tim; Han, BeomSoo; Bahado-Singh, Ray O.; Wilson, George D.; Imam, Khaled; Maddens, Michael; Graham, Stewart F. Description: Using 1H NMR metabolomics, we biochemically profiled saliva samples collected from healthy-controls (n=12), mild cognitive impairment (MCI) sufferers (n=8), and Alzheimer’s disease (AD) patients (n=9). We accurately identified significant concentration changes in 22 metabolites in the saliva of MCI and AD patients compared to controls. This pilot study demonstrates the potential for using metabolomics and saliva for the early diagnosis of AD. Given the ease and convenience of collecting…

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Altered serum levels of adipokines and insulin in probable Alzheimer’s disease

Author: Khemka, V.K.; Bagchi, D.; Bandyopadhyay, K.; Bir, A.; Chattopadhyay, M.; Biswas, A.; Basu, D.; Chakrabarti, S. Description: Cerebral hypometabolism of glucose, weight loss, and decreased food intake are characteristic features of sporadic Alzheimer’s disease (AD). A systematic study on the serum levels of adipokines and insulin, the major hormones regulating energy metabolism, food intake, and body weight, in sporadic AD is necessary. The present study compares the serum levels of leptin, adiponectin, and insulin, measured by commercially available immuno-assay kits, between controls and sporadic AD subjects. The results show…

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Targeting brain alpha7 nicotinic acetylcholine receptors in Alzheimer’s disease: rationale and current status

Author: Valles, A.S.; Borroni, M.V.; Barrantes, F.J. Description: Alzheimer’s disease (AD) is the most common form of dementia among older persons. Pathognomonic hallmarks of the disease include the development of amyloid senile plaques and deposits of neurofibrillary tangles. These changes occur in the brain long before the clinical manifestations of AD (cognitive impairment in particular) become apparent. Nicotinic acetylcholine receptors (AChRs), particularly the alpha7 subtype, are highly expressed in brain regions relevant to cognitive and memory functions and involved in the processing of sensory information. There is strong evidence that…

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Amyloid-beta peptide protects against microbial infection in mouse and worm models of Alzheimer’s disease

Author: Kumar, D.K.V.; Choi, S.H.; Washicosky, K.J.; Eimer, W.A.; Tucker, S.; Ghofrani, J.; Lefkowitz, A.; McColl, G.; Goldstein, L.E.; Tanzi, R.E.; Moir, R.D. Description: The amyloid-beta peptide (AB) is a key protein in Alzheimer’s disease (AD) pathology. We previously reported in vitro evidence suggesting that AB is an antimicrobial peptide. We present in vivo data showing that AB expression protects against fungal and bacterial infections in mouse, nematode, and cell culture models of AD. We show that AB oligomerization, a behavior traditionally viewed as intrinsically pathological, may be necessary for…

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Memory function in very early Alzheimer’s disease

Author: Petersen, R.C.; Smith, G.E.; Ivnik, R.J.; Kokmen, E.; Tangalos, E.G. Description: The detection of very early Alzheimer’s disease (AD) can be important for both theoretical and practical reasons. Typically, a memory impairment is the first sign of incipient disease, but the early clinical diagnosis can be challenging. We investigated several aspects of memory function in AD and normal aging to determine which indices of performance were most sensitive at detecting early impairments. We evaluated 106 pairs of patients with probable AD and matched controls from the Mayo Clinic Alzheimer’s…

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Stem cell therapy in Alzheimer’s disease: possible benefits and limiting drawbacks

Author: Alipour, Masoume; Nabavi, Seyed Massood; Arab, Leila; Vosough, Massoud; Pakdaman, Hossein; Ehsani, Ehsan; Shahpasand, Koorosh Description: Alzheimer’s disease (AD) is the sixth leading cause of death globally and the main reason for dementia in elderly people. AD is a long-term and progressive neurodegenerative disorder that steadily worsens memory and communicating skills eventually leads to a disabled person of performing simple daily tasks. Unfortunately, numerous clinical trials exploring new therapeutic drugs have encountered disappointing outcomes in terms of improved cognitive performance since they are not capable of halting or stimulating…

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