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The Putative Use of Lithium in Alzheimer's Disease.
Curr Alzheimer Res. 2016; 13(8):853-61.CA

Abstract

Alzheimer`s disease is a progressive neurodegenerative illness characterized by the invariant existence of β-amyloid plaques and neurofibrillary tangles. Presently approved pharmaceutical approaches offer only marginal efficacy and as yet there is no effective treatment which reverses or arrests the disease. Thus far, drugs targeting any single aspect of disease pathology have proved to be a failure or at best provided very slight clinical benefit. The consistent failure of drugs targeting aspects of the Aβ cascade has questioned the causal role of this pathway. There is a growing appreciation that the pathogenesis of the illness is multifactorial with Amyloid Beta, Phosphorylated Tau (ptau), inflammation, mitochondrial dysfunction, calcium dyshomeostasis, heavy metal imbalances, and GSK-3 interact in a highly complex manner to provoke a selfsustaining spiraling cascade of pathology, driving disease progression. In the light of such complex pathology, the failure of drugs aimed a targeting single molecules is not surprising as such approaches are usually ineffective against other complex diseases with a multifactorial pathogenesis. Combination therapies or multi target drugs might be more effective in controlling such illnesses. The putative neuroprotective effects of Lithium are achieved via the positive modulation of numerous homeostatic mechanisms regulating autophagy, oxidative stress, inflammation, and mitochondrial dysfunction likely achieved by inhibiting GSK-3 and inositol-145 triphosphate. Data regarding efficacy in human trials and animal models of AD are mixed, but recent data using "microdose" lithium in mild cognitive impairment is encouraging, hence lithium could be a putative multi target treatment in these patients. However, additional well designed long-term trials are needed to confirm its efficacy and safety, given that long term use is necessary to achieve reasonable therapeutic benefit.

Authors+Show Affiliations

No affiliation info availableIMPACT Strategic Research Centre, School of Medicine, Deakin University, P.O. Box 291, Geelong, 3220, Australia; Orygen Youth Health Research Centre and the Centre of Youth Mental Health, The Florey Institute for Neuroscience and Mental Health and the Department of Psychiatry, University of Melbourne, Parkville, 3052, Australia. MIKEBE@BarwonHealth.org.au.

Pub Type(s)

Journal Article
Review
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26892287

Citation

Morris, Gerwyn, and Michael Berk. "The Putative Use of Lithium in Alzheimer's Disease." Current Alzheimer Research, vol. 13, no. 8, 2016, pp. 853-61.
Morris G, Berk M. The Putative Use of Lithium in Alzheimer's Disease. Curr Alzheimer Res. 2016;13(8):853-61.
Morris, G., & Berk, M. (2016). The Putative Use of Lithium in Alzheimer's Disease. Current Alzheimer Research, 13(8), 853-61.
Morris G, Berk M. The Putative Use of Lithium in Alzheimer's Disease. Curr Alzheimer Res. 2016;13(8):853-61. PubMed PMID: 26892287.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Putative Use of Lithium in Alzheimer's Disease. AU - Morris,Gerwyn, AU - Berk,Michael, PY - 2015/09/10/received PY - 2015/11/01/revised PY - 2015/11/12/accepted PY - 2016/2/20/entrez PY - 2016/2/20/pubmed PY - 2017/10/3/medline SP - 853 EP - 61 JF - Current Alzheimer research JO - Curr Alzheimer Res VL - 13 IS - 8 N2 - Alzheimer`s disease is a progressive neurodegenerative illness characterized by the invariant existence of β-amyloid plaques and neurofibrillary tangles. Presently approved pharmaceutical approaches offer only marginal efficacy and as yet there is no effective treatment which reverses or arrests the disease. Thus far, drugs targeting any single aspect of disease pathology have proved to be a failure or at best provided very slight clinical benefit. The consistent failure of drugs targeting aspects of the Aβ cascade has questioned the causal role of this pathway. There is a growing appreciation that the pathogenesis of the illness is multifactorial with Amyloid Beta, Phosphorylated Tau (ptau), inflammation, mitochondrial dysfunction, calcium dyshomeostasis, heavy metal imbalances, and GSK-3 interact in a highly complex manner to provoke a selfsustaining spiraling cascade of pathology, driving disease progression. In the light of such complex pathology, the failure of drugs aimed a targeting single molecules is not surprising as such approaches are usually ineffective against other complex diseases with a multifactorial pathogenesis. Combination therapies or multi target drugs might be more effective in controlling such illnesses. The putative neuroprotective effects of Lithium are achieved via the positive modulation of numerous homeostatic mechanisms regulating autophagy, oxidative stress, inflammation, and mitochondrial dysfunction likely achieved by inhibiting GSK-3 and inositol-145 triphosphate. Data regarding efficacy in human trials and animal models of AD are mixed, but recent data using "microdose" lithium in mild cognitive impairment is encouraging, hence lithium could be a putative multi target treatment in these patients. However, additional well designed long-term trials are needed to confirm its efficacy and safety, given that long term use is necessary to achieve reasonable therapeutic benefit. SN - 1875-5828 UR - https://www.unboundmedicine.com/medline/citation/26892287/The_Putative_Use_of_Lithium_in_Alzheimer's_Disease_ DB - PRIME DP - Unbound Medicine ER -
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