Koleszterin és Alzheimer-kór

Translated title of the contribution: Cholesterol and Alzheimer's disease

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Epidemiological, biochemical and pharmacological investigations provide increasing number of evidences that altered cholesterol metabolism contributes to the development of Alzheimer's disease. The objective of the present paper is to review existing information about the links of cholesterol and amyloid metabolism from the clinical and proposed etiological viewpoins of the most frequent dementing disorder in Hungary. Beta-amyloid peptide, the major component of the senile plaques in the Alzheimer's disease brains is the end product of the abnormal post-translational processing of its precursor, called amyloid precursor protein. The compartmentation of the amyloid precursor protein molecule within the cell membrane is regulated by the cholesterol content of the bilayers. The amyloid precursor protein molecule could be present either in-, or outside of the membrane rafts. Any kind of process, which alters the compartmentation preference of the amyloid precursor protein molecule, by transfering it to the membrane rafts, favours beta- and gamma-secretase cleavage, and should be recognised as an amyloidogenic process. If the blood-brain barrier is intact, the brain is not able to take up the lipoprotein particles responsible for the transport of cholesterol. Instead of the active uptake, neurons and glial cells synthetise cholesterol de novo, in a process, where the rate limiting enzyme is 3-hydroxy-3-methylglutaryl coenzyme A. On the other hand, the brain specific CYP46A1 enzyme is responsible for the degradation of cholesterol into a water soluble metabolite, called 24S-OH cholesterol. The decreased CYP46A1 activity in the brain of Alzheimer's disease patients raises membrane cholesterol levels, and as a consequence the amyloid precursor protein is shifted and deposited in the cholesterol rich lipid rafts leading to beta-amyloid peptide specific metabolism. Among the polymorphic variants of the apolipoprotein E gene, the E4 allele is considered as a major risk factor for Alzheimer's disease. The E4 allele carrier Alzheimer's disease probands have increased amyloid burden, decreased beta-amyloid peptide degradation, and less effective neuronal repair mechanisms. Even as early as age 30, patients with Niemann-Pick Type C disease show clinical and neuropathological signs of Alzheimer's disease. The point mutation of the protein responsible for the endosomal transport of cholesterol is considered as a major cause of the beta-amyloid peptide deposition in the brain of Niemann-Pick Type C patients. One of the most exciting recent discovery, that Niemann-Pick Type C disease could be recognised as a disease model for Alzheimer's disease. New, promising cholesterol metabolism related therapeutic approaches are discussed, but it is emphasized that the clinical evidences regarding their efficacy in Alzheimer's disease are still missing.

Original languageHungarian
Pages (from-to)1903-1911
Number of pages9
JournalOrvosi Hetilap
Volume146
Issue number37
Publication statusPublished - 2005

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Alzheimer Disease
Cholesterol
Amyloid beta-Protein Precursor
Amyloid beta-Peptides
Type C Niemann-Pick Disease
Amyloid Precursor Protein Secretases
Brain
Amyloid
Membranes
Alleles
Hungary
Amyloid Plaques
Brain Diseases
Apolipoproteins E
Enzymes
Blood-Brain Barrier
Point Mutation
Neuroglia
Lipoproteins
Cell Membrane

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Koleszterin és Alzheimer-kór. / Kálmán, J.; Janka, Z.

In: Orvosi Hetilap, Vol. 146, No. 37, 2005, p. 1903-1911.

Research output: Contribution to journalArticle

Kálmán, J & Janka, Z 2005, 'Koleszterin és Alzheimer-kór', Orvosi Hetilap, vol. 146, no. 37, pp. 1903-1911.
Kálmán, J. ; Janka, Z. / Koleszterin és Alzheimer-kór. In: Orvosi Hetilap. 2005 ; Vol. 146, No. 37. pp. 1903-1911.
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