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W H Frey

Publications and source records attributed to W H Frey.

At least 19 recordsLinked to original sources
PubMed1992

Altered aspartate in Alzheimer neurofibrillary tangles.

Normal protein-bound L-aspartyl/L-asparaginyl residues may undergo post-translational modification by racemization to D-aspartate, or by isomerization to the L-isoaspartyl form in which the peptide chain links through the beta carboxyl group of the residue. Based on preliminary results reported here, proteins associated with Alzheimer neurofibrillary tangle preparations contain a significantly greater number of these modified aspartyl residues than the unaffected proteins from the surrounding gray matter or in comparable preparations from normal brains.

Aged↗
PubMed1992

Racemized D-aspartate in Alzheimer neurofibrillary tangles.

Normal protein-bound L-aspartyl/L-asparaginyl residues may undergo posttranslational modification by racemization to D-aspartate. Based on preliminary results reported here, proteins associated with Alzheimer neurofibrillary tangle preparations contain a greater number of these racemized D-aspartyl residues than the unaffected proteins from the surrounding gray matter or in comparable preparations from normal brains.

Alzheimer Disease↗
PubMed1992

Clinically diagnosed Alzheimer disease: neuropathologic findings in 650 cases.

Despite the introduction of formal clinical criteria for Alzheimer disease (AD), the clinical diagnosis of AD remains one of exclusion of other dementias. To determine the accuracy of a clinical diagnosis of AD as made by practicing physicians, we reviewed the clinicopathologic records of a dementia brain bank and summarized the literature. Of 650 demented patients diagnosed during life as having AD, at autopsy 505 (78%) had AD with or without other neuropathologic conditions; only 390 (60%) of these had AD as the only neuropathologic condition. Of the remaining 145 (22%) patients with no neuropathologic evidence of AD, 39 had the nigrostriatal changes of Parkinson disease (PD), 25 had nonspecific degenerations, 15 had Pick disease, 14 had multiple infarcts, and 11 lacked any neuropathologic abnormality. Although the overall clinical accuracy for AD was lower than that summarized from the literature, clinical accuracy improved significantly between 1986 and 1990. In our broad sample of practitioners, accuracy of clinical diagnosis of AD may be improving, but continues to be hampered by difficulty in distinguishing the dementia of AD from certain dementing conditions and from AD mixed with other neuropathologic conditions.

Aged↗
PubMed1992

A clinicopathological study of CT scans in Alzheimer's disease.

OBJECTIVE: To investigate the accuracy of cranial computerized tomography (CT) scans in distinguishing patients with Alzheimer's disease from those with other dementing conditions. DESIGN: Retrospective clinicopathological correlation with pre-mortem CT scans. SETTING: Urban and rural hospitals and nursing homes in the Upper Midwest. PATIENTS: All 507 patients had clinical dementia diagnosed as Alzheimer's disease during life and the subsequent referral of their brains to a dementia brain bank. Of these, 375 patients had had CT scans as part of the diagnostic work-up for dementia. MAIN OUTCOME MEASURES: The presence of neuropathological evidence of Alzheimer's disease and the specific findings on CT scans. RESULTS: Of the 375 patients evaluated with a CT, 28% were misdiagnosed (lacked neuropathological evidence of Alzheimer's disease); of the 132 patients evaluated without a CT scan, only 18% were misdiagnosed (P less than 0.05). The degree of atrophy and other CT findings were similar in the correctly diagnosed and misdiagnosed groups except for increased ventricular size in the correctly diagnosed patients (P less than 0.05). CONCLUSION: Although CT scans do not usually contribute to the recognition of Alzheimer's disease, the presence of ventricular enlargement may help distinguish Alzheimer's disease from other dementias.

Aged↗
PubMed1992

Risk factors in Alzheimer's disease: a clinicopathologic study.

We investigated potential risk factors for Alzheimer's disease (AD) in a clinicopathologic study of 407 patients with definite AD, 100 non-Alzheimer dementia patients, and 50 normal subjects. The AD patients had more first-degree relatives with dementia than the non-AD dementia group (odds ratio of 1.85, 95% confidence interval of 1.07-3.20) or the normal elderly (odds ratio of 3.60, 95% confidence interval of 1.50-8.64) but did not have significantly more head injuries, medical and psychiatric illnesses, or relatives with Down's syndrome. The AD patients with a family history of dementia had their dementia at a later age than those without an affected relative. These findings indicate a familial risk for AD that is greater than for other dementing illnesses and has age-related penetrance. This study does not support other putative risk factors for AD such as head trauma and familial Down's syndrome.

Aged↗
PubMed1991

Seasonal distribution of births in Alzheimer's disease.

We obtained season-of-birth data in 727 autopsy-confirmed cases of Alzheimer's Disease (AD) and compared these data with expected general population birth rates. There were no significant differences between quarterly birth rates in the AD group and expected quarterly birth rates. Edward's test for cyclical trends did not establish a peak period of birth in the AD sample. No significant differences between observed and expected quarterly birth rates were found when data were analyzed with regard to either family history of dementia or to gender. Edward's test for peak quarter was significant for AD females, however, with the peak period occurring early in the first quarter. These negative findings between observed and expected quarterly birth rates, based on the large number of autopsy-confirmed AD cases in this study, suggest that a season-of-birth effect in AD is highly unlikely.

Aged↗
PubMed1990

GM-1 treatment of Alzheimer's disease. A pilot study of safety and efficacy.

A double-blind, placebo-controlled pilot study was conducted to evaluate the safety and efficacy of treatment of patients with Alzheimer's disease using monosialoganglioside GM-1, a neurotrophic factor. Of 46 patients enrolled, 42 completed all study requirements. Nineteen patients received 100 mg of GM-1 by daily intramuscular injection for 12 weeks. Twenty-three patients received placebo. Case evaluations were done at baseline, week 12, and week 24 and included both cognitive and psychosocial scales. Study results suggested that the treatment was safe, yet offered no overall symptomatic benefit to patients with mild-to-moderate Alzheimer's disease. Whether or not GM-1 therapy may offer protective benefit by slowing or arresting the progression of the disease remains unclear, since the results of the cognitive evaluations suggested that neither the GM-1 group nor the placebo group declined significantly during the 24-week study.

Affect↗
PubMed1990

Immunogold labeling of Alzheimer paired helical filaments with ganglioside MAB A2B5.

The ganglioside monoclonal antibody A2B5 has previously been used at the light microscopic level to label Alzheimer neurofibrillary tangles (NFTs). Light microscopic analysis, however, could not reveal whether the A2B5 antibody-labeled NFTs or membrane fragments associated with NFTs. Therefore, we used pre-embedding immunohistochemical electron microscopy to examine A2B5 labeling of NFT. We found that the A2B5 antibody does indeed label a NFT antigen associated with the paired helical filament (PHF) structure, while no significant labeling of membranes or membrane fragments was observed. However, no clear periodicity of the immunogold label on the PHF was found.

Alzheimer Disease↗
PubMed1990

Dementia lacking distinctive histologic features: a common non-Alzheimer degenerative dementia.

From a series of 460 dementia patients referred to a regional brain bank, 14 (3%) patients had a pathologic diagnosis of primary degeneration of the brain involving multiple sites (frontoparietal cortex, striatum, medial thalamus, substantia nigra, and hypoglossal nucleus), with cell loss and astrocytosis. There were no neuronal inclusions and essentially no senile plaques. This entity, which we have termed "dementia lacking distinctive histology" (DLDH), presented with memory loss and personality changes, and led to death, usually within 2 to 7 years. Dysarthria and dysphagia were prominent in the later phases of the illness in most patients. The psychometric findings of some of the patients were consistent with a "frontal" lobe dementia. A few patients had prominent caudate atrophy on CT as well as neuropathologically. Eight of our patients had positive family histories for neurologic disease, mainly dementia. DLDH, in addition to Pick's disease, is a major member of the frontal-lobe dementia group. In patients under age 70 years, the frontal lobe dementias represent an important diagnostic consideration.

Aged↗
PubMed1987

D-aspartate in human brain.

The presence of the biologically uncommon D-aspartic acid (D-aspartate) in human brain white matter has been previously reported. The earlier study has now been expanded to include D/L-aspartate ratios from 67 normal brains. The data show that the D-aspartate content increases rapidly from 1 year to approximately 35 years of age, levels off in middle age, and then appears to decrease somewhat. The D-aspartate content in gray matter remains at a consistently low level (half of that found in white matter) throughout the human life span. Within the limitations of current analytical methods, there was no detectable difference in D/L-aspartate ratios in white and gray matter of brains with Alzheimer's disease and several other pathologies when compared with brains of normal subjects. However, the presence of a significant D-aspartate level in white matter during the adult life span may lead to changes in protein configuration related to dysfunctions associated with the aging brain.

Adolescent↗
PubMed1987

Ganglioside monoclonal antibody (A2B5) labels Alzheimer's neurofibrillary tangles.

Ganglioside monoclonal antibody (A2B5) labels Alzheimer's neurofibrillary tangles both in isolated neurofibrillary tangle-bearing nerve cells and in partially purified preparations of tangle fibers. Antibody staining was preabsorbed by preincubation of antibody with neuronal ganglioside preparations. These results suggest that Alzheimer's neurofibrillary tangles have a ganglioside associated with them.

Alzheimer Disease↗
PubMed1985

Human brain tubulin purification: decrease in soluble tubulin with age.

The soluble tubulin of human cerebral cortex, as assessed by [3H]colchicine binding of the 100,000 g supernatant fraction, decreases drastically with age, 75 percent from age 0 to age 90. There is also a considerably lower concentration of high molecular weight proteins in the soluble fraction of postmortem human cerebral cortex than in that of nonhuman species. Human brain tubulin can be polymerized into microtubules with DEAE-dextran. The DEAE-dextran induced microtubules are stable to cold temperature (4 degrees) and calcium. However, in the presence of 1 M glutamate, the microtubules become cold labile and depolymerize at 4 degrees. Thus we have developed a novel method for purifying polymerization competent tubulin from fresh or frozen human cerebral cortex. Human brain tubulin purified by our novel method is very similar to tubulin from the brains of other mammals in molecular weight, amino acid composition, polymerization-depolymerization parameters, and structural dimensions of the microtubules formed.

Adolescent↗
PubMed1985

Glial fibrillary acidic protein and Alzheimer's disease.

A major protein associated with Alzheimer's disease (AD) was detected by an electrophoretic study of temporal cortex obtained at autopsy from patients affected with AD, non-AD dementia, and normal controls matched for age and sex. A markedly increased amount of a 50,000 dalton molecular weight protein, which has been identified as glial fibrillary acidic protein (GFAP), was observed in the crude nuclear fraction of temporal cortex from AD patients. These electrophoretic data may reflect the presence of GFAP immunopositive astrocytic processes that have been shown by immunocytologic methods to infiltrate the neurofibrillary tangles that characterize AD.

Alzheimer Disease↗