Publication Date:
2010-09-11
Description:
Amyloid-beta (Abeta) peptides, derived from the amyloid precursor protein, and the microtubule-associated protein tau are key pathogenic factors in Alzheimer's disease (AD). How exactly they impair cognitive functions is unknown. We assessed the effects of Abeta and tau on axonal transport of mitochondria and the neurotrophin receptor TrkA, cargoes that are critical for neuronal function and survival and whose distributions are altered in AD. Abeta oligomers rapidly inhibited axonal transport of these cargoes in wild-type neurons. Lowering tau levels prevented these defects without affecting baseline axonal transport. Thus, Abeta requires tau to impair axonal transport, and tau reduction protects against Abeta-induced axonal transport defects.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024010/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024010/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vossel, Keith A -- Zhang, Kai -- Brodbeck, Jens -- Daub, Aaron C -- Sharma, Punita -- Finkbeiner, Steven -- Cui, Bianxiao -- Mucke, Lennart -- AG011385/AG/NIA NIH HHS/ -- C06 RR018928/RR/NCRR NIH HHS/ -- NS041787/NS/NINDS NIH HHS/ -- NS057906/NS/NINDS NIH HHS/ -- R00 NS057906/NS/NINDS NIH HHS/ -- R00 NS057906-05/NS/NINDS NIH HHS/ -- R01 AG011385/AG/NIA NIH HHS/ -- R01 AG011385-07/AG/NIA NIH HHS/ -- R01 NS041787/NS/NINDS NIH HHS/ -- R01 NS041787-09/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2010 Oct 8;330(6001):198. doi: 10.1126/science.1194653. Epub 2010 Sep 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA. kvossel@gladstone.ucsf.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20829454" target="_blank"〉PubMed〈/a〉
Keywords:
Amyloid beta-Peptides/*metabolism/pharmacology
;
Animals
;
*Axonal Transport
;
Cells, Cultured
;
Hippocampus/cytology
;
Mice
;
Mitochondria/metabolism
;
Neurons/*metabolism
;
Peptide Fragments/*metabolism/pharmacology
;
Receptor, trkA/metabolism
;
tau Proteins/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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