Alterations in calcium content and biochemical processes in cultured skin fibroblasts from aged and Alzheimer donors.

Abstract

Aging and Alzheimer disease lead to alterations in several biochemical properties of cultured skin fibroblasts. Total bound calcium increases in fibroblasts due to normal aging (+52%) and is elevated even further with Alzheimer disease (+197%). Processes that require mitochondrial function, such as glucose and glutamine oxidation, declined in cells from aged donors (-25%) and decreased even further in Alzheimer disease (-46%). In addition, biosynthetic processes that depend upon mitochondrial function, such as glucose or glutamine incorporation into protein and lipid, paralleled the oxidative decreases. Cytosolic and nuclear processes such as leucine incorporation into protein and thymidine into DNA were depressed more by aging than Alzheimer disease. These findings suggest that calcium homeostasis and mitochondrial functions are altered more by Alzheimer disease than normal aging.

Increased Proteolytic Activity in Erythrocytes from Patients with Alzheimer's Disease

“…Stimu lation of the lymphocytes revealed a marked sensitivity of the cells from the Alzheimer patients to temporarily increased intracellular free Ca levels [5]. Results obtained from cultured skin fibroblasts from Alzheimer patients have shown an increased amount of total bound Ca [3] but a decreased level of free Ca [4], It has also been observed that the degree of degrada tion of the anion transport protein (band 3) in erythro cytes as well as the rate of spectrin degradation in cultured fibroblasts (which may be calpain dependent) arc in creased from aged and Alzheimer donors [ 19,20], In the latter study, no differences were found in the total activi ties of calpains or calpastatin. These results may possibly be a consequence of a Ca-induced binding of calpains to the cell membranes from Alzheimer patients.…”

“…Aging and Alzheimer's disease arc correlated with changes in Ca homeostasis in different non-neuronal cells [2][3][4][5] as well as in hippocampal neu rons [6], An unregulated level of free Ca in the cytosol may induce changes in Ca-dependent proteolytic systems in neuronal as well as non-neuronal cells.…”

Mitochondrial DNA A4336G Mutation in Alzheimer’s and Parkinson’s Diseases

“…Platelet complex activity was found to be significantly lower in PD patients than in controls [7, 8]. Similarly, AD patients have shown complex IV abnormalities in platelets [9]as well as abnormalities in the mitochondrial respiratory-chain complex in the neocortex [10]and fibroblasts [11]. …”

Amyloid enhancing factor activity is associated with ubiquitin

“…Although AD was first thought to be a disease characterized by a brain-limited amyloidosis (Ogomori et al 1989, Scudiero et al 1986, Peterson and Goldman 1986, Zubenko et al 1987), Joachim and others (1989) have lately reported the detection of amyloid B-protein (G1enner and Wong 1984a) or A4 (Masters et al 1985a) deposits in non-neuronal tissues of AD patients including skin, subcutaneous tissue and intestine. Thus, amyloidosis in AD is systemic in nature.…”