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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Chronic stress as a risk factor for Alzheimer’s disease: Roles of microglia-mediated synaptic remodeling, inflammation, and oxidative stress

Bisht, K., Sharma, K., Tremblay, M.E. (2018) Neurobiology of Stress, 9, 9-21 Microglia are the predominant immune cells of the central nervous system (CNS) that exert key physiological roles required for maintaining CNS homeostasis, notably in response to chronic stress, as well as mediating synaptic plasticity, learning and memory. The repeated exposure to stress confers a higher risk of developing neurodegenerative diseases including sporadic Alzheimer’s disease (AD). While microglia have been causally linked to amyloid beta (Abeta) accumulation, tau pathology, neurodegeneration, and synaptic loss in AD, they were also attributed…

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Prevention of Alzheimer’s disease

Author: Szekely, C.A.; Breitner, J.C.S.; Zandi, P.P. Description: The already considerable public health burden of Alzheimer’s disease will likely worsen as populations around the world age. As a result, there is considerable motivation to develop effective strategies for preventing the disease. A wide variety of such strategies are under investigation and include pharmaceuticals, nutriceuticals, diet, physical activity and cognitive activity. We review here the most promising candidates and the epidemiologic evidence for their efficacy. Although none of these have yet to be definitively shown to prevent Alzheimer’s disease, further research…

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Fibrinogen Induces Microglia-Mediated Spine Elimination and Cognitive Impairment in an Alzheimer’s Disease Model

Author: Merlini, M.; Rafalski, V.A.; Rios Coronado, P.E.; Gill, T.M.; Ellisman, M.; Muthukumar, G.; Subramanian, K.S.; Ryu, J.K.; Syme, C.A.; Davalos, D.; Seeley, W.W.; Mucke, L.; Nelson, R.B.; Akassoglou, K. Description: Cerebrovascular alterations are a key feature of Alzheimer’s disease (AD) pathogenesis. However, whether vascular damage contributes to synaptic dysfunction and how it synergizes with amyloid pathology to cause neuroinflammation and cognitive decline remain poorly understood. Here, we show that the blood protein fibrinogen induces spine elimination and promotes cognitive deficits mediated by CD11b-CD18 microglia activation. 3D molecular labeling in…

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Exercise plays a preventive role against Alzheimer’s disease

Author: Radak, Z., Hart, N., Sarga, L., Koltai, E., Atalay, M., Ohno, H., & Boldogh, I. Description: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder affecting the elderly population. It is predicted that the incidence of AD will be increased in the future making this disease one of the greatest medical, social, and economic challenges for individuals, families, and the health care system worldwide. The etiology of AD is multifactorial. It features increased oxidative state and deposition of amyloid plaques and neurofibrillary tangles of protein tau in the central cortex…

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Comparison of memory fMRI response among normal, MCI, and Alzheimer’s patients

Author: Machulda, M.M.; Ward, H.A.; Borowski, B.; Gunter, J.L.; Cha, R.H.; O’Brien, P.C.; Petersen, R.C.; Boeve, B.F.; Knopman, D.; Tang-Wai, D.F.; Ivnik, R.J.; Smith, G.E.; Tangalos, E.G.; Jack, C.R.J. Description: OBJECTIVE: To determine whether an fMRI memory encoding task distinguishes among cognitively normal elderly individuals, patients with mild cognitive impairment (MCI), and patients with early Alzheimer’s disease (AD). METHODS: Twenty-nine subjects (11 normal, 9 MCI, 9 AD) were studied with an fMRI memory encoding task. A passive sensory task was also performed to assess potential intergroup differences in fMRI responsiveness….

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Gender-specific neuroimmunoendocrine aging in a triple-transgenic 3xTg-AD mouse model for Alzheimer’s disease and its relation with longevity

Gimenez-Llort, L., Arranz, L., Mate, I., De la Fuente, M. (2008) Neuroimmunomodulation, 15(4-6), 331-343 In the present work, we briefly review the evidence on the key role played by the neuroimmunoendocrine network in the etiopathogenesis of Alzheimer’s disease (AD) and provide new behavioral, immune and endocrinological data obtained on old male and female triple-transgenic 3xTg-AD mice harboring PS1(M146V), APP(Swe) and tau(P301L) transgenes in contrast to wild-type animals. The results indicate that several aspects of the impairment of the neuroimmunoendocrine network that occurs with aging are more evident in the 3xTg-AD…

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Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer’s disease

Author: Moreno-Jiménez, E. P., Flor-García, M., Terreros-Roncal, J., Rábano, A., Cafini, F., Pallas-Bazarra, N., Ávila, J., & Llorens-Martín, M. Description: The hippocampus is one of the most affected areas in Alzheimer’s disease (AD). Moreover, this structure hosts one of the most unique phenomena of the adult mammalian brain, namely, the addition of new neurons throughout life. This process, called adult hippocampal neurogenesis (AHN), confers an unparalleled degree of plasticity to the entire hippocampal circuitry. Nonetheless, direct evidence of AHN in humans has remained elusive. Thus, determining whether new neurons are…

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Meditation and Music Improve Memory and Cognitive Function in Adults with Subjective Cognitive Decline: A Pilot Randomized Controlled Trial

Author: Innes, Kim E.; Selfe, Terry Kit; Khalsa, Dharma Singh; Kandati, Sahiti Description: BACKGROUND: While effective therapies for preventing or slowing cognitive decline in at-risk populations remain elusive, evidence suggests mind-body interventions may hold promise. OBJECTIVES: In this study, we assessed the effects of Kirtan Kriya meditation (KK) and music listening (ML) on cognitive outcomes in adults experiencing subjective cognitive decline (SCD), a strong predictor of Alzheimer’s disease. METHODS: Sixty participants with SCD were randomized to a KK or ML program and asked to practice 12 minutes/day for 3 months,…

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