摘要:

Summary:We studied the relationship of numbers of neurofibrillary tangles (NFTs) in selected cortical and subcortical sites to the duration of clinical disease and severity of dementia. Sixteen patients with a clinical diagnosis of “probable” Alzheimer disease were screened with standardized neuropsychological instruments to estimate the severity of dementia. Tissues were obtained at autopsy from the subiculum, four neocortical areas, and the nucleus basalis of Meynert; NFT counts were assessed with the thioflavin S stain. Overall, the subiculum showed the most NFTs, followed by visual association and premotor cortices, primary cortex (motor and visual), and the nucleus basalis. NFT counts were significantly positively correlated with the duration of disease in the nucleus basalis and less strongly in the motor cortex. Neuropsychological impairment was significantly correlated with NFT counts only in the nucleus basalis. In turn, counts in the nucleus basalis were reliably correlated with those in all other brain regions except the subiculum. Counts in the subiculum showed no correlation with any other area. Numbers of NFTs within functionally related sites, the primary motor and premotor cortices or primary and visual association cortices, were significantly or near-significantly correlated, whereas motor and visual cortical counts showed no intercorrelation. Our results indicate that although there is less NFT accumulation in the nucleus basalis than in many other brain regions, counts in this structure bear a close relationship to disease severity and duration and to NFT accumulation in other regions.

ISSN:0893-0341    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The dementia of Alzheimer disease (AD) correlates with the deposition of extracellular amyloid, and this amyloid arises from the abnormal processing of a high molecular weight amyloid peptide precursor (APP), which is a normal cellular protein that is found in both brain and in peripheral tissues in humans. Overproduction of the APP in AD could cause increased concentrations of this protein in either human blood or cerebrospinal fluid (CSF). However, thus far no direct demonstration of soluble APP in human blood has been possible, owing to poor assay sensitivity and interfering plasma proteins. These two problems were eliminated with the present development of an extracting two-site immunoradiometric assay (IRMA). Two rabbit polyclonal antisera were prepared reacting to two different sites (amino acids 161–180 and 597–624) of the APP molecule. The near N-terminal antiserum (anti-APP161–180) was covalently coupled to a solid phase support and the near C-terminal directed antiserum (anti-APP597–624) was indirectly labeled using125labeled near C-terminal synthetic peptide corresponding to amino acids 597–624. The IRMA was validated by partial purification of the APP from human serum and demonstration of the protein's molecular weight (112 kDa) by Western immunoblot procedures. Results of the IRMA showed that the APP is present in human plasma (mean ± SE concentration=32 ± 6 pM, n=25), and there was no significant difference in the APP concentration in 25 controls, 19 patients with AD, and 10 individuals with Down syndrome (DS). Immunoreactive APP was generally not detectable in control or AD CSF volumes as large as 1 ml. In conclusion, these studies provide the first demonstration of the presence of APP in human blood that is immunoreactive with an antiserum directed against the amyloidotic portion (i.e., amino acids 597–624) of the APP molecule. In addition, these studies show that soluble APP is present in human blood, but that its concentration is not increased in AD.

ISSN:0893-0341    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Summary:Many of the actions of potassium channel blockers, such as 4-aminopyridine, appear to complement the deficits in Alzheimer disease. The two clinical studies in the literature are contradictory, so potassium channel blockers may still merit trial in Alzheimer disease.

ISSN:0893-0341    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Summary:In Alzheimer disease (AD) the “primum movens” is amyloid (AM) production within the cerebral cortex. Cerebral AM alone may be asymptomatic. Clinical symptoms (amnesia, instrumental disorders) appear when AM induces neighboring neuritic alterations: paired hellical filaments (PHF), and distant neuronal body lesions: neurofibrillary tangles (NFT), i.e. pathologic synthesis of abnormal proteins. The timing for these inductions should be equal to the survival after the onset of amnesia: a mean of 14 months for the induction of the peri-AM neuritic alterations and a mean of 52 months for the induction of the distant to AM NFT in the hippocampic neuronal bodies. We postulate that the AM induces this neuronal pathology by producing functional zinc deficiency. The hippocampal zinc decreases in AD. The mechanism of the AM-induced zinc deficiency may be the following: the AM is formed within the walls of capillaries (senile plaques), disturbs the blood-brain barrier (BBB) and toxic metals (i.e., iron, aluminum, mercury) may enter in the cerebral cortex, where they displace the zinc in some enzymes. NFT and neuronal dysfunction may be produced by deficiency of the following zinc enzymes: (a) those of DNA metabolism, inducing abnormal DNA in the neurons and therefore abnormal protein synthesis, PHF-NFT; (b) those of glutamate (GLU) dehydrogenase (which catabolizes GLU), resulting in an excitotoxic increase of GLU; (c) those of neuronal detoxification, superoxydedismutase, carbonic anhydrase, and lactate dehydrogenase leading to neuronal toxicity. During the window between AM formation and PHF-NFT production (14-52 months), a zinc complex crossing the BBB may be useful to prevent AM of producing PHF-NFT, and also to normalize neuronal detoxification. By the zinc treatment, AM should remain asymptomatic and clinical dementia should be prevented.

ISSN:0893-0341    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Summary:A German family with 21 members affected by Alzheimer disease (AD) was studied clinically and genetically. The diagnosis was histologically verified in three affected family members. Ancestors were traced through seven generations to a couple residing in East-Westfalia during the middle of the 19th century. Dementia was often accompanied by extrapyramidal features and myoclonus. No cases of Down syndrome or hematologic malignancy occurred in this family. Clinical manifestations, temporal progression, neurological testing, and neuropathological features do not differ from the more common sporadic form of AD. The inheritance pattern is most consistent with autosomal-dominant transmission.

ISSN:0893-0341    

出版商:OVID    

年代:1991

数据来源: OVID

ISSN:0893-0341    

出版商:OVID    

年代:1991

数据来源: OVID

ISSN:0893-0341    

出版商:OVID    

年代:1991

数据来源: OVID

ISSN:0893-0341    

出版商:OVID    

年代:1991

数据来源: OVID

ISSN:0893-0341    

出版商:OVID    

年代:1991

数据来源: OVID

ISSN:0893-0341    

出版商:OVID    

年代:1991

数据来源: OVID