Alzheimer risk factors age and female sex induce cortical Aβ aggregation by raising extracellular zinc
Aging and female sex are the major risk factors for Alzheimer's disease and its associated brain amyloid-beta (A beta) neuropathology, but the mechanisms mediating these risk factors remain uncertain. Evidence indicates that A beta aggregation by Zn(2+)released from glutamatergic neurons contri...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2020
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| Sorozat: | MOLECULAR PSYCHIATRY
25 No. 11 |
| doi: | 10.1038/s41380-020-0800-y |
| mtmt: | 31341681 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/19322 |
| LEADER | 02299nab a2200325 i 4500 | ||
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| 005 | 20211025160307.0 | ||
| 008 | 200810s2020 hu o 0|| zxx d | ||
| 022 | |a 1359-4184 | ||
| 024 | 7 | |a 10.1038/s41380-020-0800-y |2 doi | |
| 024 | 7 | |a 31341681 |2 mtmt | |
| 040 | |a SZTE Publicatio Repozitórium |b hun | ||
| 041 | |a zxx | ||
| 100 | 1 | |a Datki Zsolt László | |
| 245 | 1 | 0 | |a Alzheimer risk factors age and female sex induce cortical Aβ aggregation by raising extracellular zinc |h [elektronikus dokumentum] / |c Datki Zsolt László |
| 260 | |c 2020 | ||
| 300 | |a 2728-2741 | ||
| 490 | 0 | |a MOLECULAR PSYCHIATRY |v 25 No. 11 | |
| 520 | 3 | |a Aging and female sex are the major risk factors for Alzheimer's disease and its associated brain amyloid-beta (A beta) neuropathology, but the mechanisms mediating these risk factors remain uncertain. Evidence indicates that A beta aggregation by Zn(2+)released from glutamatergic neurons contributes to amyloid neuropathology, so we tested whether aging and sex adversely influences this neurophysiology. Using acute hippocampal slices, we found that extracellular Zn2+-elevation induced by high K(+)stimulation was significantly greater with older (65 weeks vs 10 weeks old) rats, and was exaggerated in females. This was driven by slower reuptake of extracellular Zn2+, which could be recapitulated by mitochondrial intoxication. Zn2+:A beta aggregates were toxic to the slices, but A beta alone was not. Accordingly, high K(+)caused synthetic human A beta added to the slices to form soluble oligomers as detected by bis-ANS, attaching to neurons and inducing toxicity, with older slices being more vulnerable. Age-dependent energy failure impairing Zn(2+)reuptake, and a higher maximal capacity for Zn(2+)release by females, could contribute to age and sex being major risk factors for Alzheimer's disease. | |
| 700 | 0 | 1 | |a Oláh Zita |e aut |
| 700 | 0 | 2 | |a Jánosi-Mózes Emese |e aut |
| 700 | 0 | 2 | |a Szegedi Viktor |e aut |
| 700 | 0 | 2 | |a Kálmán János |e aut |
| 700 | 0 | 2 | |a Hunya Ákos |e aut |
| 700 | 0 | 2 | |a Fülöp Lívia |e aut |
| 700 | 0 | 2 | |a Tamano Haruna |e aut |
| 700 | 0 | 2 | |a Takeda Atsushi |e aut |
| 700 | 0 | 2 | |a Adlard Paul A. |e aut |
| 700 | 0 | 2 | |a Bush Ashley I. |e aut |
| 856 | 4 | 0 | |u http://publicatio.bibl.u-szeged.hu/19322/1/s41380-020-0800-y.pdf |z Dokumentum-elérés |