Extraneuronal Manifestations of Alzheimer's Disease

Scott, Robert B.

doi:10.1111/j.1532-5415.1993.tb06704.x

Cited by 30 publications

(8 citation statements)

References 88 publications

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“…Moreover, a number of alter-tempted to inhibit cysteine proteinases and to identify ations were reported to occur also in several nonner-the enzymes which might be responsible for alterations. vous tissues (Scott, 1993) Results presented herein describe how TK-ab were (0.4 mM final concentration) as basically reported by Bajkoswki and Frankfater (1975). Volume in the cudownmodulated by the action of cysteine proteinase inhibitors, NH 4 Cl, and KCl.…”

mentioning

confidence: 75%

Cysteine proteinases are responsible for characteristic transketolase alterations in Alzheimer fibroblasts

1997

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Cultured fibroblasts from patients affected by Alzheimer's disease (AD) exhibited peculiar alterations of the enzyme transketolase (TK). Abnormalities (dubbed alkaline bands, ab) consisted of enzyme forms having unusually high pl and were proposed as a marker of the disease in living patients. The mechanisms of TK-ab expression were investigated with the use of cysteine proteinase inhibitors and purified preparations of either rat liver or human cysteine proteinases. The cysteine proteinase inhibitors N-acetyl-leu-leu-norleucinal (ALLN), L-trans-Epoxy-succinyl-leucylamido(4-guanidino)butane (E-64), and egg white cystatin added to AD cells just prior to extraction abolished TK abnormalities. Moreover, 1 day incubation of AD cultures with either ALLN (10 micrograms/ml), NH4Cl (10 mM), or KCl (30 mM) prevented TK-ab generation, due, presumably, to an impairment of lysosomal functions. Isolated rat liver cysteine proteinases were able to degrade TK in normal extracts and reproduce the characteristic TK-ab of AD fibroblasts. Moreover, pure human cathepsin H was also shown to partially induce an Alzheimer-like TK pattern and cleave normal TK to a 35 kDa fragment as spontaneously occurring in AD fibroblasts. The explanation of mechanisms of TK-ab formation provided evidence for an underlying imbalance of proteolysis in AD fibroblasts due to a relative increase/derangement of the cysteine proteinases cathepsins which might be also involved in the reported abnormal processing of multiple cellular components.

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confidence: 75%

Cysteine proteinases are responsible for characteristic transketolase alterations in Alzheimer fibroblasts

1997

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“…An increasing amount of evidence also indicates that AD is in fact a systemic disorder manifesting itself in numerous abnormalities in non-neural tissues, e.g., in blood and skin cells (65,66). The first 2-DE study in which cells of non-neuronal origin were investigated suggested an abnormal expression of actin in lymphocytes (67).…”

Section: -De Studies In Admentioning

confidence: 96%

Problems Associated with Biological Markers of Alzheimer’s Disease

Frey¹,

Mattila

Korolainen

et al. 2005

Neurochem Res

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The etiopathogenesis of Alzheimer's disease (AD) is still unclear, although clinical diagnostic criteria exist and the neuropathology of AD has been studied in great detail during the last 20 years. The present study addresses certain problems in the search for biological markers for the diagnosis, as well as in the follow-up of the course of AD and its differential diagnosis and reports some of our own observations in comparison with other studies. These include protein, genetic and neuroimaging markers. The definitions of biological markers and search strategies are also discussed.

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“…This has resulted in the hypothesis that Aß protein produces the abnormalities seen in the endothelium, and plays a key role in AD development. AD has been viewed Age,years 198 Dement Geriatr Cogn Disord 2000; 11:197-201 McGleenon/Passmore/McAuley/Johnston as a systemic disorder with a number of peripheral abnormalities such as membrane changes in erythrocytes, platelets and leucocytes, abnormal immune function and biochemical abnormalities [10]. Aß protein has been detected in peripheral perivascular sites such as the skin, gastrointestinal tract, and olfactory mucosa [10,11].…”

Section: Introductionmentioning

confidence: 99%

“…AD has been viewed Age,years 198 Dement Geriatr Cogn Disord 2000; 11:197-201 McGleenon/Passmore/McAuley/Johnston as a systemic disorder with a number of peripheral abnormalities such as membrane changes in erythrocytes, platelets and leucocytes, abnormal immune function and biochemical abnormalities [10]. Aß protein has been detected in peripheral perivascular sites such as the skin, gastrointestinal tract, and olfactory mucosa [10,11]. Skin vessel reactivity has been shown to be impaired in AD patients [12] which some have interpreted as supporting the hypothesis of AD as a systemic disease.…”

Section: Introductionmentioning

confidence: 99%

No Evidence of Endothelial Dysfunction in Patients with Alzheimer’s Disease

McGleenon

Passmore

McAuley³

et al. 2000

Dement Geriatr Cogn Disord

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In view of accumulating evidence of vascular pathology in Alzheimer’s disease (AD), we tested the hypothesis that AD patients have impaired endothelial function. This was assessed using the technique of strain-gauge venous occlusion plethysmography, which measures forearm blood flow (FBF). Intra-arterial (brachial) infusion of acetylcholine (ACh) and sodium nitroprusside (SNP) was used to assess local endothelial dependent and independent responses, respectively. There was no difference in the basal FBF of patients and controls. ACh and SNP caused dose-related increases in FBF from baseline, but no difference was recorded between the AD and control group. This study provides no evidence of endothelial dysfunction in the systemic circulation of patients with AD.

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Extraneuronal Manifestations of Alzheimer's Disease

Cited by 30 publications

References 88 publications

Cysteine proteinases are responsible for characteristic transketolase alterations in Alzheimer fibroblasts

Cysteine proteinases are responsible for characteristic transketolase alterations in Alzheimer fibroblasts

Problems Associated with Biological Markers of Alzheimer’s Disease

No Evidence of Endothelial Dysfunction in Patients with Alzheimer’s Disease

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