ISSN:0893-0341    

出版商:OVID    

年代:1992

数据来源: OVID

ISSN:0893-0341    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Summary:New molecular information about Alzheimer disease (AD) is appearing at an unprecedented rate. Much interest centers on the βA4 amyloid protein, which is progressively deposited in senile plaques and blood vessels in AD brain tissue. The discovery that some kindreds with familial AD have a mutation in the gene coding for the βA4 amyloid precursor protein (APP) suggests that this mutation alone may be sufficient to cause the full spectrum of clinical and pathological changes that characterize AD. Although APP point mutations may turn out to be relatively rare causes of AD, the idea that accelerated βA4 deposition is an early and critical event in many patients continues to gain support from studies in humans, animals, and cultured cells. Identification of the biochemical steps leading to production of the βA4 peptide from APP is now a critical issue. Recent reports indicate that normal lysosomal processing pathways can produce carboxyl-terminal fragments of APP that contain the entire βA4 sequence, and are therefore potentially amyloidogenic. The mechanisms by which such intermediate forms are further processed and released, resulting in extracellular βA4 deposits in plaques and vessels, are yet to be determined. It is likely that full elucidation of the βA4–producing pathways will ultimately yield new therapeutic approaches to this complex and tragic disorder.

ISSN:0893-0341    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Summary: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.

ISSN:0893-0341    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Summary:Patients with dementia of the Alzheimer type (DAT) reportedly have reduced concentrations and function of some brain messengers, particularly acetylcholine and somatostatin, not only in the cerebral cortex, but also in subcortical structures, e.g., the hippocampus and the hypothalamus. We wished to determine the responsive pattern of DAT patients to neurohormonal and pharmacologic probes affecting growth hormone (GH) release through an interaction with hypothalamic cholinergic and somatostatineergic (SS) neurons. In 10 DAT patients, pyridostigmine (120 mg orally, p.o.), an inhibitor of acetylcholinesterase, induced an increase in GH levels similar to that elicited by the drug in age-matched controls. In 9 DAT patients, administration of GH-releasing hormone (GHRH, 1 μg/kg body weight, intravenously, i.v.) induced an increase in plasma GH not different from that evidenced in control subjects. In DAT patients the GHRH-induced GH increase was completely inhibited by pretreatment with atropine (1 mg intramuscularly, i.m., 15 min before administration of GHRH). These findings are considered to indicate that in DAT patients, hypothalamic cholinergic and somatostatinergic neurons involved in control of somatotropic function are preserved.

ISSN:0893-0341    

出版商:OVID    

年代:1992

数据来源: OVID

ISSN:0893-0341    

出版商:OVID    

年代:1992

数据来源: OVID

ISSN:0893-0341    

出版商:OVID    

年代:1992

数据来源: OVID

ISSN:0893-0341    

出版商:OVID    

年代:1992

数据来源: OVID

ISSN:0893-0341    

出版商:OVID    

年代:1992

数据来源: OVID

ISSN:0893-0341    

出版商:OVID    

年代:1992

数据来源: OVID