{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T20:11:21Z","timestamp":1779912681107,"version":"3.53.1"},"reference-count":24,"publisher":"S. Karger AG","issue":"5","license":[{"start":{"date-parts":[[1999,1,1]],"date-time":"1999-01-01T00:00:00Z","timestamp":915148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[1999,1,1]],"date-time":"1999-01-01T00:00:00Z","timestamp":915148800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gerontology"],"published-print":{"date-parts":[[1999]]},"abstract":"<jats:p>&lt;i&gt;Background:&lt;\/i&gt; The recent, magnificent results of molecular biology concerning \u03b2-amyloid (\u03b2A) metabolism in early onset Alzheimer\u2019s disease (AD) have generated a series of new findings and, in turn, a new etiological concept. Attention on the early events in the pathogenesis of AD has been shifted from the chromosomal abnormalities in the nucleus of nerve cells onto genetic changes in the mitochondrial genome. This offers a new pathogenetic approach which also opens new pharmacological challenges particularly for the episodic forms of AD. &lt;i&gt;Objective:&lt;\/i&gt; Alterations occurring at the mitochondrial genome result in major consequences of oxidative phosphorylation and, if a specific threshold is exceeded, they may constitute important causative events in the apoptosis of selected nerve cells. The fact that the main source of mitochondrial metabolism is its glucose turnover allows monitoring brain changes in glucose metabolism by 18F-2 deoxyglucose positron emission tomography. In the demented brain, a low glucose turnover causes a cholinergic deficit by decreasing the synthetic rate of acetyl coenzyme A (AcCoA). AcCoA represents the key substrate for the acetylation of choline to acetylcholine by choline acetyltransferase. The consistent energy need for AcCoA synthesis appears obvious when considering that 1 molecule of glucose generates just 2 molecules of AcCoA, but 38 molecules of ATP. In the brain, AcCoA is exclusively synthesized in the glycolitic pathway. Generation of \u03b2A is increased if the synthetic rate of ATP drops below a critical threshold: under these conditions, the \u03b2A precursor protein (\u03b2APP) is inserted only in part into synaptic membranes which have the highest \u03b2APP turnover. In conditions of short ATP supply, \u03b2APP is not split at the \u03b2 region by an ATP-activated protease and this results in a substantial increase in uncleaved \u03b2A molecules. &lt;i&gt;Conclusion:&lt;\/i&gt; Peroxidative alterations in mitochondrial DNA are of importance in degenerative diseases of postmitotic tissues, particularly in degenerative diseases. This offers a new pharmacological approach for the treatment of AD. Neurotrophic factors and estrogen seem to be the first pharmacological leads.<\/jats:p>","DOI":"10.1159\/000022104","type":"journal-article","created":{"date-parts":[[2003,4,15]],"date-time":"2003-04-15T17:26:45Z","timestamp":1050427605000},"page":"289-297","source":"Crossref","is-referenced-by-count":17,"title":["Mitochondrial Genome Lesions in the Pathogenesis of Sporadic Alzheimer\u2019s Disease"],"prefix":"10.1159","volume":"45","author":[{"given":"W.A.","family":"Meier-Ruge","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Bertoni-Freddari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[1999,8,25]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1038\/27351"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1038\/353844a0"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5293.1710"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1038\/nm0896-864"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5381.1303"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5381.1309"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1159\/000022031"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3932(91)90084-L"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(93)91320-R"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(93)90955-M"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4943(91)90032-L"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1016\/0047-6374(80)90120-7"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4943(84)90007-4"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4943(91)90022-I"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1038\/ng1292-324"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(94)90079-5"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(82)90223-2"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(94)90136-8"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(80)90220-7"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1993.1672"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(89)90055-6"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(94)90033-7"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1016\/0197-0186(94)90064-7"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5391.1072"}],"container-title":["Gerontology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/22104","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/22104","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T04:41:19Z","timestamp":1745469679000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000022104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999]]},"references-count":24,"journal-issue":{"issue":"5","published-online":{"date-parts":[[1999,10,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000022104","archive":["Portico"],"relation":{},"ISSN":["0304-324X","1423-0003"],"issn-type":[{"value":"0304-324X","type":"print"},{"value":"1423-0003","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999]]}}}