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Biomedical subjects

R N Rosenberg

Publications and source records attributed to R N Rosenberg.

At least 19 recordsLinked to original sources
PubMed2003

Correlation of statin-increased platelet APP ratios and reduced blood lipids in AD patients.

Platelets, like neurons, contain 120- to 130- and 110-kd amyloid precursor proteins (APPs). Their ratio is reduced in AD, further reductions correlating with reduced Mini-Mental Status Examination scores [r(11) = 0.69, p < 0.05]. As statins alter APP processing, platelet APPs were analyzed in patients with AD given anticholesterol drugs for 6 weeks. APP ratios increased [t(37) = -3.888, p = 0.0004], proportionally with reduced cholesterol [r(36) = -0.45, p = 0.005]. Longer trials may reveal slowed cognitive loss, validating this index.

Alzheimer Disease↗
PubMed2001

Platelet APP isoform ratios in asymptomatic young adults expressing an AD-related presenilin-1 mutation.

The Alzheimer's disease (AD) related amyloid precursor protein (APP) is stored, cleaved and released similarly from neurons and from platelets. We have reported that the proportion of 120-130 to 110 kDa carboxyl-cleaved APP present in the platelets of AD patients is significantly lower than that of platelets of age-matched controls. This reduced APP isoform ratio, not seen in several other disease groups, is further reduced as the severity of AD increases. Since the neuropathology of AD is believed to begin many years before the onset of cognitive loss, we have also compared platelet APP ratios of four pre-symptomatic young adults carrying a presenilin-1 mutation to seven siblings homozygous for the normal PS-1 gene in an effort to determine whether reduced APP ratios are present before apparent cognitive loss in familial AD. Decreased platelet APP ratios were not seen in any of these subjects at this time. We will continue to monitor these subjects as they near the mean age of AD onset in these families. As the magnitude of the APP ratio reduction is proportional to the severity of cognitive loss in sporadic AD, these cognitively normal incipient AD subjects would not be expected to present significant reductions in this AD severity index at this time. Alternatively, the absence of platelet APP ratio reductions may result from a failure of platelets from familial PS-1 AD subjects to manifest altered APPs, as has been reported for PS-2 AD subjects, unlike those of sporadic AD patients. Continued monitoring of cognitive status in our sub-set of controls with AD-like low APP ratios may yet validate the ability of this assay to detect incipient sporadic AD.

Adult↗
PubMed2001

Effects of practice on category fluency in Alzheimer's disease.

Evaluation of patients with suspected Alzheimer's disease (AD) often involves clinicians of multiple disciplines working in collaboration to maximize diagnostic accuracy. Accordingly, repeated administrations of some common tests of mental status may occur within a relatively brief time period. The effect of such retesting on subsequent results is largely unknown for many cognitive tasks, despite the possibility that repeated administrations may artificially inflate scores. To assess the potential impact of practice effects on a commonly administered verbal fluency task, animal naming was administered twice within a 1-week period to 111 patients with probable AD and 12 persons without dementia. Non-demended subjects were the only group to demonstrate a small (3 point), but statistically significant practice effect. Regardless of level of cognitive impairment, patients with AD did not show significant practice effects over repeated administrations of animal naming after a relatively brief test-retest interval, suggesting the robust nature of this task in AD.

Aged↗
PubMed2001

Comparison of the hopkins verbal learning test-revised to the California verbal learning test in Alzheimer's disease.

We examined the validity of the revised Hopkins Verbal Learning Test (HVLT-R) by comparing performances on the HVLT-R and the California Verbal Learning Test (CVLT) in participants with Alzheimer's disease (AD). Total learning, delayed recall, intrusion errors, and recognition performance were significantly related across tests, but the number of perseverative responses showed no linear association. Despite similar results across measures, some of the variables were only modestly correlated, which may reflect differences in test procedures and the limited range of scores for some variables. Furthermore, the HVLT-R may not be challenging enough to elicit some of the types of recall errors commonly seen in AD to the same extent as the CVLT Nonetheless, the HVLT-R shows promise for providing a multidimensional assessment of verbal learning and memory and may be ideal in cases where brief assessment ofmemory and/or serial evaluations are needed.

Aged↗
PubMed2000

Platelet APP isoform ratios correlate with declining cognition in AD.

BACKGROUND: Platelets and neurons both contain large quantities of two carboxyl-truncated 120 to 130 and 110 kDa Alzheimer amyloid precursor proteins (APPs). Platelets taken from patients with AD have been reported to contain a reduced ratio of these APPs. OBJECTIVE: To further study the AD specificity of reduced platelet APP ratios and to determine whether, after 3 years, cognitive losses in AD are accompanied by similarly reduced platelet APP ratios. METHODS: To test the AD specificity of reduced platelet APP ratios, we quantitated these APPs in eight patients with PD and six patients with hemorrhagic stroke (HS). To determine whether further cognitive losses correlate with platelet APP ratio reductions in patients with AD, the authors re-examined platelet APPs and Mini-Mental State Examination (MMSE) scores of 10 patients with AD and 11 controls, who were tested 3 years ago. APP ratios were determined by the average of six assays using Western blotting with m22C11 monoclonal antibody, enhanced chemoluminescence, and digital scanning of autoradiographs. RESULTS: APP ratios were normal in the patients with PD and HS, further supporting the AD specificity of this assay. After 3 years, the MMSE scores and APP ratios of our control subjects changed by <4%. However, the average MMSE scores of our patients with AD declined from 16.4 to 8.3, and their average 120 to 130/110 kDa APP ratios declined from 5.8 to 3.6. The difference between AD and control APP ratios, with no overlap, is significant and the correlation between the 3-year decline in AD MMSE scores and reduced APP ratios (r = 0.69) was significant. CONCLUSIONS: Although the number of subjects analyzed was limited, reduced platelet APP ratios appear to be a specific biological marker of AD and a biological index of the severity of cognitive loss in AD.

Aged↗
PubMed2000

Apoptosis and neurologic disease.

Many neurological disorders involve cell death. During development of the nervous system, cell death is a normal feature. Elimination of substantial numbers of initially generated cells enables useful pruning of "mismatched" or excessive cells produced by exuberance during the proliferative and migratory phases of development. Such cell death, occurring by "programmed" pathways, is termed apoptosis. In mature organisms, cells die in two major fashions, either by necrosis or apoptosis. In the adult nervous system, because there is little cell production during adulthood, there is little normal cell death. However, neurological disease is often associated with significant neural cell death. Acute disorders, occurring over minutes to hours, such as brain trauma, infarction, hemorrhage, or infection, prominently involve cell death, much of which is by necrosis. Chronic disorders, with relatively slow central nervous system degeneration, may occur over years or decades, but may involve cell losses. Such disorders include motor neuron diseases such as amyotrophic lateral sclerosis (ALS), cerebral dementing disorders such as Alzheimer's disease and frontotemporal dementia, and a variety of degenerative movement disorders including Parkinson's disease, Huntington's disease, and the inherited ataxias. There is evidence that the mechanism of neuronal cell death in these disorders may involve apoptosis. Direct conclusive evidence of apoptosis is scarce in these chronic disorders, because of the swiftness of cell death in relation to the slowness of the disease. Thus, at any particular time point of assessment, very few cells would be expected to be undergoing death. However, it is clearly of importance to define the type of cell death in these disorders. Of significance is that while treating the underlying causes of these conditions is an admirable goal, it may also be possible to develop productive therapies based on alleviating the process of cell death. This is particularly likely if this cell loss is through apoptosis, a programmed process for which the molecular cascade is increasingly understood. This article reviews our understanding of apoptosis in the nervous system, concentrating on its possible roles in chronic neurodegenerative disorders.

Apoptosis↗
PubMed2000

Comparison of the CERAD and CVLT list-learning tasks in Alzheimer's disease.

This investigation examined the relationship of the word list from the CERAD neuropsychological battery to the California Verbal Learning Test (CVLT) in a sample of 138 subjects with Probable Alzheimer's disease (AD). Results revealed modest but statistically significant associations between the two measures on many key variables. Total words learned showed the strongest association, with lower correlations for delayed recall, intrusion errors, and recognition variables. As expected, the CERAD and CVLT assess similar aspects of verbal learning in patients with AD. However, the modest level of many of the correlations suggests that caution should be exercised in applying the same interpretive strategies derived on more comprehensive measures to shorter ones.

Adult↗