Expression of αB-crystallin in Alzheimer's disease

B-crystallin is a member of the small heatshock protein family. Under pathological conditions, the expression of B-crystallin increases in proliferating astrocytes, which suggests that this protein, in addition to glial fibrillary acidic protein (GFAP), can be a marker for gliosis in neurodegenerative diseases. Immunoblotting and immunohistochemical methods were used for the detection of B-crystallin in the brains of Alzheimer's disease (AD) patients and nondemented controls. An increase in B-cyrstallin expression was found in the brains of AD patients. Immunoreaction was present in reactive astrocytes, microglia, and oligodendrocytes, indicating that all types of glia respond to the stress associated with AD pathology. Colocalization of GFAP and B-crystallin was found in fibrous astrocytes. However, the intensity and range of B-crystallin expression appeared to be limited as compared with the large increase in the number of GFAP-positive astrocytes. This indicates that expression of B-crystallin is not a marker for gliosis in AD. Immunoreactivity to B-crystallin in both astrocytes and microglia was found mainly restricted to areas with senile plaques and neurofibrillary tangles, suggesting the association of B-crystallin with amyloid deposition in AD.Supported by a grant (No. EY08202) from the National Institutes of Health, Bethesda, USASupported by a fellowship of the Royal Netherlands Academy of Arts and Sciences     

Amnestic MCI or prodromal Alzheimer's disease?

The concept of mild cognitive impairment (MCI) draws attention to cognitive changes not severe enough to warrant the diagnosis of dementia. As used today, it covers many pathological disorders and characterises a diverse population of patients who attend memory clinics. Our concern is the underlying heterogeneity. We suggest that it will soon be possible (if it is not already) to identify the underlying pathological disorders before the affected patients meet the criteria of dementia, thanks to specific neuropsychological assessments, neuroimaging, and biomarkers. In particular, patients with Alzheimer's disease (AD), the most important subgroup of patients with MCI, can already be identified before appearance of the fully developed clinical dementia syndrome. Accordingly, this paper proposes diagnostic criteria for "prodromal AD".     

Resveratrol--a boon for treating Alzheimer's disease?

Resveratrol, a red wine polyphenol, is known to protect against cardiovascular diseases and cancers, as well as to promote antiaging effects in numerous organisms. It also modulates pathomechanisms of debilitating neurological disorders, such as strokes, ischemia, and Huntington's disease. The role of resveratrol in Alzheimer's disease is still unclear, although some recent studies on red wine bioactive compounds suggest that resveratrol modulates multiple mechanisms of Alzheimer's disease pathology. Emerging literature indicates that mechanisms of aging and Alzheimer's disease are intricately linked and that these mechanisms can be modulated by both calorie restriction regimens and calorie restriction mimetics, the prime mediator of which is the SIRT1 protein, a human homologue of yeast silent information regulator (Sir)-2, and a member of NAD+-dependent histone deacetylases. Calorie restriction regimens and calorie restriction-mimetics trigger sirtuins in a wide variety of organisms, ranging from bacteria to mouse. In a mouse model of Huntington's disease, resveratrol-induced SIRT1 was found to protect neurons against ployQ toxicity and in Wallerian degeneration slow mice, resveratrol was found to protect the degeneration of neurons from axotomy, suggesting that resveratrol may possess therapeutic value to neuronal degeneration. This paper mainly focuses on the role of resveratrol in modulating AD pathomechanisms.     

Cholesterol,Aβ and Alzheimer's disease

Statins have been used for many years for the treatment of hypercholesterolemia. They lower low-density lipoprotein (LDL) cholesterol, increase high-density lipoprotein (HDL) levels and are considered to be very safe. Recently, a set of potential new applications was identified for statins. In the future, these drugs could be used to treat Alzheimer's disease (AD). Past studies have suggested a link between AD and lipids and a series of reports has recently been published that significantly tightens this link and also provides some explanations at the cellular level. This review focuses on these recent developments and perspectives that appear to link cholesterol, β-amyloid and AD.     

Is Alzheimer's disease a synaptic disorder?

BACKGROUND: In Alzheimer's disease (AD), the common symptom is loss of memory. Learning and memory are associated with amoeboid movements of synaptic endings. Docosahexaenoic acid (DHA) is a major lipid constituent of synaptic end sites. Minor changes in the fluidity of phospholipidic membranes have a dramatic impact on the function of synapses, where membrane fluidity may influence the neurotransmitter receptor activity. METHOD: Studies pertaining to the role of DHA as a neuroprotective agent was reviewed. RESULTS: Here we will show a conceptual framework for the role of DHA in the prevention of AD. The DHA content has been shown to be decreased in the brain and plasma of patients affected by AD. Aspirin triggers the generation of DHA-derived mediators that are themselves neuroprotective. CONCLUSION: Adequate dietary intakes of the neuroprotective DHA (and aspirin?) may slow down the progression of AD. An essential reserve of synapses from early development is needed.     

Alzheimer's disease: cholesterol a menace?

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease manifested by cognitive and memory deterioration, culminating in a spectrum of neuropsychiatric disturbances and the impairment of daily activities. AD is a multifactorial disease with a range of contributing factors which includes genes and diet. The magnitude of AD is reflected in the loss of individuality of the affected person and in the terminal course through which the disease develops. In this review, we aim to provide a background on AD and the contribution of cholesterol in the etiology of Alzheimer's. Cholesterol seems to be intimately linked with the generation of amyloid plaques, which is central to the pathogenesis of AD. Although there are conflicting reports on the role of cholesterol in AD, majority of the studies point out the positive association of cholesterol with AD.     

When is category specific in Alzheimer's disease?

Mixed findings have emerged concerning whether category-specific disorders occur in Alzheimer's disease. Factors that may contribute to these inconsistencies include: ceiling effects/skewed distributions for control data in some studies; differences in the severity of cognitive deficit in patients; and differences in the type of analysis (in particular, if and how controls are used to analyse single case data).We examined picture naming in Alzheimer's patients and matched elderly healthy normal controls in three experiments. These experiments used stimuli that did and did not produce ceiling effects/skewed data in controls. In Experiment 1, we examined for category effects in individual DAT patients using commonly used analyses for single cases (chi2 and z-scores). The different techniques produced quite different outcomes. In Experiment 2a, we used the same techniques on a different group of patients with similar outcomes. Finally, in Experiment 2b, we examined the same patients but (a) used stimuli that did not produce ceiling effects/skewed distributions in healthy controls, and (b) used statistical methods that did not treat the control sample as a population. We found that ceiling effects in controls may markedly inflate the incidence of dissociations in which living things are differentially impaired and seriously underestimate dissociations in the opposite direction. In addition, methods that treat the control sample as a population led to inflation in the overall number of dissociations detected. These findings have implications for the reliability of category effects previously reported both in Alzheimer patients and in other pathologies. In particular, they suggest that the greater proportion of living than nonliving deficits reported in the literature may be an artifact of the methods used.     

Is cholesterol a culprit in Alzheimer's disease?

A pivotal role for cholesterol influence on production of the putative AD toxin, amyloid beta (Abeta), has been amply demonstrated. More importantly, this relationship has consistently been identified in both in vivo and in vitro studies. Lowering cholesterol levels has been shown to cause a beneficial effect on Abeta levels in animal models, and epidemiological data indicate a beneficial effect on the risk of AD with prior statin use. Blinded, placebo-controlled clinical investigations assessing the benefit of statins on cognitive indices in mild to moderate AD are ongoing and one will be reported on soon. A prospective study assessing the effect of statin use on the risk of AD is under way as an observational component of a placebo-controlled primary prevention trial testing anti-inflammatory agents. Nevertheless, the foregoing suggests that routine monitoring and intervention for elevated cholesterol levels among the elderly could promote more than a healthy heart.