The concentrations of 17 elements in the nail and hair of 117 subjects from a nonindustrialized environment were determined by instrumental neutron activation analysis (INAA). A new method of statistical treatment that allows for more meaningful use of detection limit values was used to process the concentration data. Geometric means and standard errors are presented for each element, along with a summary of the effects of age, sex, and treatment on the concentration of each element. For nails, these data represent the first comprehensive study for several important elements. Correlations for each element between hair and nail were determined. With few exceptions, concentrations of nonessential trace elements were positively correlated in hair and nail, whereas concentrations of essential elements showed no correlations. The factors affecting concentrations and control levels must be considered in studying alterations in disease states.

Adolescent↗

PubMedDate not supplied

Trace elements in Alzheimer's disease pituitary glands.

Levels of mercury (Hg), selenium (Se), iron (Fe), rubidium (Rb), and zinc (Zn) were measured in the pituitary gland to assess the possibility of a potential difference in the environmental Hg exposure of Alzheimer's disease (AD) patients and control subjects and levels of other elements of interest in AD. The pituitary gland has been established as a good predictor of environmental Hg exposure. Neutron activation analysis was utilized to determine levels of these elements in pituitary glands of 43 AD subjects and 15 control subjects. No significant differences were observed between the AD and control means for these five elements. The sole significant Pearson's correlation involving Hg was the established correlation with Se, indicative of the detoxification of Hg. The absence of a statistical difference between AD and control pituitary gland Hg levels suggests AD patients do not have an excessive environmental exposure to Hg compared to controls.

Aged↗

PubMedDate not supplied

A search for longitudinal variations in trace element levels in nails of Alzheimer's disease patients.

Levels of Br, Hg, K, and Zn were determined by INAA in the nails of Alzheimer's disease (AD) patients at 6-mo intervals for up to 3 yr. These elements have been shown to be imbalanced in AD nail. Bromine showed no trends. Mercury tended to decrease in nail with increasing age of patient, and with the duration and severity of the dementia. Potassium and Zn tended to increase with these same factors. Hence, progressive changes in trace-element levels do occur in AD nail, although imbalances are detected even in the earliest sampled stages of the disease.

Age Factors↗

PubMedDate not supplied

Time-dependence of, and effects of inhibition and cellular aging on, chloride efflux across erythrocyte membranes in Huntington's disease.

Previous studies have demonstrated an increased rate of chloride transport across erythrocyte membranes in Huntington's disease, a process regulated at the external side of the major transmembrane protein Band 3. A marked effect of time was noted in 3 Huntington's disease samples that were studied more than 4 h after obtaining the blood. In order to study anion transport more closely in Huntington's disease and the apparent time-dependence of chloride efflux in this disorder, we have performed several sets of experiments. Chloride transport in Huntington's disease erythrocytes was found to be extremely sensitive to time with the efflux rate constant decreasing by approximately 30% over a 24 h period. Chloride transport in control cells was unaffected by time. Inhibition studies with the specific anion transport blocker 4,4'-diisothiocyanto-2,2'-disulfonic acid stilbene (DIDS) demonstrated that the same degree of inhibition of chloride transport could be achieved at a much lower concentration of DIDS in Huntington's disease than in controls. Comparison of chloride efflux in fractions enriched in young and old erythrocytes, respectively, obtained by density centrifugation of fresh blood, demonstrated that only in the young fraction of cells was chloride efflux diminished with time in Huntington's disease. Chloride transport in in vivo aged Huntington's cells or both young and old control cells was essentially not dependent on time. These results are discussed in terms of proposed molecular mechanisms for neuronal loss in this disorder. The alterations in chloride efflux in extraneural erythrocytes are consistent with a proposed cell-surface membrane defect involving a protein in Huntington's disease.

Adult↗

PubMedDate not supplied

Cortical senile plaques in coronary artery disease, aging and Alzheimer's disease.

Mild alterations in cognitive function are present in normal aging and severe cognitive alterations are a hallmark of Alzheimer's disease (AD). The cognitive change in AD has been correlated to the characteristic pathologic lesions in the brain, senile plaques (SP) and neurofibrillary tangles. Senile plaques are the most consistent correlative marker in AD. We present preliminary data indicating that abundant SP are found in the brains of nondemented patients dying with or as a result of critical coronary artery disease (cCAD) compared to nonheart disease (non-HD) subjects; 15 of 20 cCAD patients contained SP and only two of 16 non-HD patients contained SP.

Aged↗

PubMedDate not supplied

31P magnetic resonance spectroscopy in Alzheimer's and Pick's disease.

Previous studies have suggested a defect in phosphorus metabolism in Alzheimer's disease (AD) gray matter. We have studied phosphorus metabolites in both gray and white matter in autopsy specimens of nine subjects with late-stage AD, three with Pick's disease and seven age-matched controls. Phosphorus metabolites sugar phosphate (SU), phosphomonoester (PME), phosphodiester (PD), and inorganic phosphate (PI) were quantified as mole percentages in regional neocortical specimens using nuclear magnetic resonance spectroscopy. Senile plaque (SP) and neurofibrillary tangle (NFT) counts were determined in adjacent cortical sections. In the inferior parietal lobule gray and white matter, mole percentage normalized PME, and PD were significantly greater than control values in both AD and Pick's disease. A significant correlation was found between PD and NFT in AD parietal gray matter. Our data indicates that phosphorus metabolite alterations are present in two cortical degenerative diseases and are not likely to be specific for AD.

Aged↗

PubMedDate not supplied

Characterization of brain samples in studies of aging, Alzheimer's, and other neurodegenerative diseases.

We review current understanding of the clinical and pathologic information needed for the determination of optimal brain tissue samples for the conduct of studies of Alzheimer's disease (AD). Characteristics that may distinguish AD from other dementing disorders are discussed. Selected considerations in the conduct of basic neurobiological studies are also outlined. Although the 28 NIA-funded Alzheimer's Centers can provide excellent clinical and neuropathological data, studies conducted outside these centers should also strive to gather the information suggested here. Clinical and neuropathological data should be used not only to classify subjects as control or AD, but also as variables that may significantly contribute to the analysis of neurobiological data obtained in the laboratory.

Aging↗

PubMedDate not supplied

Morphometric image analysis of neuropil threads in Alzheimer's disease.

Neuropil threads were quantitated in the neuropil (excluding senile plaques) of the superior frontal gyrus of 6 late stage patients with Alzheimer's disease (AD) and 6 age-matched control subjects using tau immunocytochemistry and computerized morphometric image analysis. The mean percent of the area of the neuropil occupied by neuropil threads was 10.6 for AD and 0.19 for controls (p < 1 x 10(-10)). The mean length of neuropil threads in AD was 21.9 mu compared with 19.7 mu for controls (p < 1 x 10(-10)). The mean area of neuropil threads was 25.3 mu 2 for AD and 21.3 mu 2 for controls (p < 1 x 10(-10)). In AD, the threads were most prominent in mid cortex (lamina 2 and 3) and least prominent in the lower cortex (lamina 5 and 6). Neuropil threads appear to lead to severe disorganization of intracortical and corticocortical connectivity and probably play a role in the cognitive failure in AD.

Aged↗

PubMedDate not supplied

Carboxy terminal of beta-amyloid deposits in aged human, canine, and polar bear brains.

Immunocytochemistry, using antibodies specific for different carboxy termini of beta-amyloid. A beta 40 and A beta 42(43), was used to compare beta-amyloid deposits in aged animal models to nondemented and demented Alzheimer's disease human cases. Aged beagle dogs exhibit diffuse plaques in the absence of neurofibrillary pathology and the aged polar bear brains contain diffuse plaques and PHF-1-positive neurofibrillary tangles. The brains of nondemented human subjects displayed abundant diffuse plaques, whereas the AD cases had both diffuse and mature (cored) neuritic plaques. Diffuse plaques were positively immunostained with an antibody against A beta 42(43) in all examined species, whereas A beta 40 immunopositive mature plaques were observed only in the human brain. Anti-A beta 40 strongly immunolabeled cerebrovascular beta-amyloid deposits in each of the species examined, although some deposits in the polar bear brain were preferentially labeled with anti-A beta 42(43). beta-amyloid deposition was evident in the outer molecular layer of the dentate gyrus in the aged dog, polar bear, and human. Within this layer, A beta 42 was present as diffuse deposits, although these deposits were morphologically distinct in each of the examined animal models. In dogs, A beta 42 was cloud-like in nature; the polar bear demonstrated a more aggregated type of deposition, and the nondemented human displayed well-defined deposits. Alzheimer's disease cases were most frequently marked by neuritic plaques in this region. Taken together, the data indicate that beta-amyloid deposition in aged mammals is similar to the earliest stages observed in human brain. In each species, A beta 42(43) is the initially deposited isoform in diffuse plaques.

Aged↗

PubMedDate not supplied

Acrolein is increased in Alzheimer's disease brain and is toxic to primary hippocampal cultures.

Accumulating evidence implicates oxidative stress in the pathogenesis of several neurodegenerative diseases including Alzheimer's disease (AD). Increased lipid peroxidation, decreased levels of polyunsaturated fatty acids, and increased levels of 4-hydroxynonenal (HNE), F(2)-isoprostanes, and F(4)-neuroprostanes are present in the brain in AD. Acrolein, an alpha,beta-unsaturated aldehydic product of lipid peroxidation, is approximately 100 times more reactive than HNE and recently was demonstrated in neurofibrillary tangles in the brain in AD. In three brain regions of 10 AD patients compared with 8 age-matched control subjects, we found increased mean extractable acrolein, with the increases reaching statistical significance in the amygdala and hippocampus/parahippocampal gyrus. In hippocampal neuron cultures, acrolein was neurotoxic in a time- and concentration-dependent manner and more toxic than HNE at 5 microM concentrations of each. Acrolein exposure led to a significant concentration-dependent increase in intracellular calcium concentrations. Collectively, these data show that acrolein is increased in the brain in AD and demonstrate neurotoxicity mechanisms that might be important in the pathogenesis of neuron degeneration in AD.

Acrolein↗

PubMedDate not supplied

Comparison of neuropathologic criteria for the diagnosis of Alzheimer's disease.

The National Institute on Aging and Reagan Institute (NIA-RI) criteria, and other neuropathologic criteria for Alzheimer's disease (AD), were compared with the clinical diagnosis of dementia in a well defined population of Catholic sisters. The 47-participant subset examined in this study were college educated and lacked complicating conditions such as brain infarcts or diffuse Lewy body disease. Sixteen participants had a clinical diagnosis of dementia. The NIA-RI criteria imply a perfect correlation between neuritic plaque (NP) density and neurofibrillary tangle distribution. However, NP density often did not coincide with tangle distribution. As a result, it was not possible to categorize many of the participants using the NIA-RI guidelines. The 'high likelihood' category of the NIA-RI criteria for AD research settings (neocortical Braak stage and frequent neocortical NP) had relatively high specificity (90% of nondemented participants did not meet this criteria). However, only half of the demented participants were in this category. Neuropathologic criteria requiring the presence of neocortical tangles (rather than neocortical Braak stage) had relatively high sensitivity, accounting for 87-94% of participants with dementia, but also included 32-35% of nondemented participants. Criteria based on neocortical NP or senile plaques had 100% sensitivity, but a majority of nondemented participants also met these criteria. The results support consideration of both tangles and NP for the neuropathologic diagnosis of AD, but indicate that refinement of the NIA-RI criteria is necessary. A possible refinement is suggested for further consideration.

Aged↗

PubMedDate not supplied

Neuropathological criteria for the diagnosis of Alzheimer's disease.

The definitive diagnosis of Alzheimer's disease (AD) is made at autopsy by the presence of abundant neuritic plaques (NP) and neurofibrillary tangles (NFT) in the neocortex, entorhinal cortex, and hippocampus. The two criteria most frequently used by neuropathologists for the diagnosis of AD over the past 12 years are those described by Khachaturian and the Consortium to Establish a Registry for Alzheimer's Disease. Though both have been useful, they have weaknesses and lack validation. The majority of recent studies has shown that NFT in the entorhinal cortex, hippocampus, and neocortex and NP in the neocortex correlate best with severity of dementia in AD. The criteria recommended by the Workshop on Diagnostic Criteria for the Neuropathological Assessment of AD uses semiquantitation of NFT and NP in the neocortex, adds evaluation of the hippocampus and entorhinal cortex, places emphasis on coexisting lesions such as vascular lesions and Lewy bodies, and establishes criteria for general pathologists and more rigorous criteria for the AD research setting. These criteria will require further refinement and validation.

Aged↗

PubMedDate not supplied

Elevated 4-hydroxynonenal in ventricular fluid in Alzheimer's disease.

4-Hydroxynonenal (4-HNE), an aldehyde by-product of the peroxidation of fatty acids, has been shown to have toxic properties for neurons in culture. In light of increasing evidence that oxidative stress contributes to the neurodegenerative process in Alzheimer's disease (AD), we quantified levels of free and protein-bound 4-HNE in the ventricular fluid from 19 AD subjects and 13 control subjects by high-pressure liquid chromatography and dot-blot immunoassay. Free 4-HNE levels were found to be significantly elevated in the ventricular fluid of AD subjects compared with control subjects (p = 0.0096). These results demonstrate increased lipid peroxidation in AD brain and suggest a role for 4-HNE in the neurodegenerative process.

Aged↗