Zaven S. Khachaturian

The role of calcium regulation in brain aging: reexamination of a hypothesis

Studies of the central nervous system have a long history; however, it is only recently that we have begun to understand brain function in health and disease states. And, the topic of the aging brain has become a subject of intense study for a short period. At present, the process of normal aging is relatively poorly understood. Although there are a number of theories of aging, no single theory appears to account for most age-dependent brain changes. This review provides a re-evaluation of the “Calcium Hypothesis of Brain Aging” in light of new evidence which supports the proposition that cellular mechanisms, which maintain the homeostasis of cytosol Ca2+ concentration, play a key role in brain aging; and that sustained changes in [Ca2+]i homeostasis provide the final common pathway for age-associated brain changes. This revision of the calcium hypothesis suggests that there is a complex interaction between the amount of [Ca2+]i perturbation and the duration of such deregulation of Ca2+ homeostasis and it proposes that a small disturbance in Ca2+ homeostasis with a sustained increase in [Ca+]i over a long period has similar cell injuring consequences as that produced by a large increase in [Ca2+]i over a shorter period. Although there are several alternative mechanisms through which the regulation of cytosol [Ca2+]i can be disrupted (such as changes in ion channels, extrusion pumps, and sequestration), this review focuses on disruptions in energy metabolism and changes in the structure and function of membranes as the most likely antecedent events which lead to disruption of Ca2+ homeostasis. The principle purpose of this review is to identify scientific opportunities and stimulate further research into cellular mechanisms of brain aging.

Alzheimer's disease : cause(s), diagnosis, treatment, and care

IntroductionA Synthesis of Critical Topics in Alzheimers Disease, Z.S. Khachaturian and T.S. RadebaughOverview and Historic PerspectivesCurrent Research on Alzheimers Disease in an Historical Perspective, R. KatzmanA History of the Morphology of Alzheimers Disease, R.D. TerryEpidemiologyPutative Risk Factors for Alzheimers Disease, R. MayeuxDescriptive Epidemiology of Alzheimers Disease, D.A. EvansMethods of Screening for Survey Research on Alzheimers Disease and Related Dementias, B.J. GurlandDiagnosisDifferential Diagnosis of Alzheimers Disease, J.C. MorrisClinical Assessment of Patient with Dementia, S. GilmanHeterogeneity of Alzheimers Disease, A. HeymanThe Use of Tests and Instruments in the Evaluation of Patients with Dementia, R.C. MohsBiological MarkersThe Neuropathology of Alzheimers Disease: Diagnostic Features and Standardization, S.S. Mirra and W.R. MarkesberyPathology, Neurobiology, and Animal Models of Alzheimers Disease, J.C. Troncoso, B.J. Crain, S.S. Sisodia, and D.L. PriceNeuroimaging Applications for the Study of Alzheimers Disease, T.F. BudingerCause(s)Intrinsic Biological Aging as Underlying Pathogenetic Mechanism, G.M. MartinCerebral Metabolic Impairments, J.P. BlassThe Metabolism of Apolipoprotein E and the Alzheimers Diseases, A.D. RosesNeuroimmune Mechanisms in the Pathogenesis of Alzheimers Disease, P.L. McGeer and E.G. McGeerCauses of Alzheimers Disease, A.B. YoungTrace Elements in Alzheimers Disease, W.R. MarkesberyTreatmentClinical Drug Trials in Alzheimers Disease: Methodological Considerations, L.J. ThalPharmacological Approaches to Behavioral Symptoms in Alzheimers Disease, D. GalaskoTreatment of Alzheimers Disease, L. Shihabuddin and K.L. DavisPsychosocial Interventions, M.S. Mittelman and S.H. FerrisCare and ManagementInappropriate Behavior, J. Cohen-MansfieldManaging Problems in Dementia Patients: Depression and Agitation, L. TeriOverview of Psychosocial Factors Contributing to Stress of Family Caregivers, K.C. BuckwalterThe Influence of Social Context on the Caregiving Experience, R.J.V. MontgomeryCare for Families Facing Alzheimers Disease: Primary Care Practice Implications from Research, L.P. GwytherIndex

Aluminum toxicity among other views on the etiology of Alzheimer disease

Abstract This commentary proposes that aluminum toxicity must be viewed as only one among several co-factors in the etiology of Alzheimer disease. It provides a brief overview of the major clusters of studies concerned with identifying the cause(s) of this disorder.

Overview of basic research on Alzheimer disease: Implications for cognition

Summary:During the past 12 years, research on the etiology of Alzheimer disease (AD) has made dramatic advances. Although we still do not have a clear picture of what factor(s) cause AD, growing evidence indicates that the fundamental problem in AD is associated with the death of neurons. The purpose of this article is to re-evaluate in detail how the regulation of intracellular free calcium might play a critical role in cell death and in the expression of AD neuropathology. There is an urgent need to find means to ameliorate the symptoms of AD and ways to slow the progression of the disease process. Unfortunately, AD appears to be a very complex neurochemical puzzle

A Unifying Hypothesis on the Etiology of Alzheimer’s Disease

In recent years, it has become increasingly evident that the fundamental scientific issues concerning the etiology of Alzheimer’s disease (AD) should focus on the search for mechanisms of cell dysfunction and selective neuronal loss. It is now well established that the structural and functional changes in neurons occur in specific regions of the AD brain.

Status of Alzheimer Disease Research

Since its inception in 1974, the National Institute on Aging (NIA), the Federal agency with the prime responsibility for conducting and supporting research on the biomedical and behavioral processes of aging and the diseases of aging, has targeted Alzheimer’s disease (AD) as one of the most important research priorities and challenges. Within the Public Health Service (PHS) of the Department of Health and Human Services (HHS), the NIA shares an interest and responsibility for this research with its sister institutes, the National Institute of Allergy and Infectious Diseases; and the National Institute of Mental Health, ADAMHA.