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Lithium may be useful in the prevention of Alzheimer's disease in individuals at risk of presenile familial Alzheimer's disease.
Med Hypotheses. 2008 Dec; 71(6):948-51.MH

Abstract

Alzheimer's disease (AD) is the most common form of dementia among older people. Presenile familial AD (FAD) and sporadic Alzheimer's disease (SAD) have identical brain lesions, containing senile plaques with beta-amyloid (Abeta) peptide and neurofibrillary tangles formed by hyperphosphorylation of a microtubule-associated protein known as tau. However, FAD and SAD differ in onset and genetic transmission. Unlike SAD, presenile FAD is transmitted as a pure autosomal dominant trait. The authors suggest that lithium could be used for AD prevention, particularly in individuals at risk of presenile FAD, which has early onset. Evidence supporting this hypothesis suggests that lithium decreases Abeta peptide production and inhibits the activity of glycogen synthase kinase-3 which induces aggregation of tau protein into tangles, and tau hyperphosphorylation. Prevalence of AD is lower in patients with chronic lithium treatment, which also increases brain-derived neurotrophic factor activity, so might prevent onset in patients at risk for AD. Several considerations are suggested for prevention trials: the effect of lithium could be evaluated in young animal models that express presenile FAD mutant genes; the time, dose, duration and monitoring of lithium therapy are considered; early phenotypes could be monitored for treatment effect; and some other agents, like valproic acid, could also be candidates for prevention.

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Authors+Show Affiliations

Yeh HL
Department of Family Medicine, Taipei Veterans General Hospital, Taiwan.
Tsai SJ
No affiliation info available

MeSH

Age of OnsetAgedAlzheimer DiseaseAmyloid beta-PeptidesBrainGlycogen Synthase Kinase 3HumansLithium CompoundsMiddle AgedMutationPeptide FragmentsPrevalence

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18760542

Citation

Yeh, Heng-Liang, and Shih-Jen Tsai. "Lithium May Be Useful in the Prevention of Alzheimer's Disease in Individuals at Risk of Presenile Familial Alzheimer's Disease." Medical Hypotheses, vol. 71, no. 6, 2008, pp. 948-51.
Yeh HL, Tsai SJ. Lithium may be useful in the prevention of Alzheimer's disease in individuals at risk of presenile familial Alzheimer's disease. Med Hypotheses. 2008;71(6):948-51.
Yeh, H. L., & Tsai, S. J. (2008). Lithium may be useful in the prevention of Alzheimer's disease in individuals at risk of presenile familial Alzheimer's disease. Medical Hypotheses, 71(6), 948-51. https://doi.org/10.1016/j.mehy.2008.03.049
Yeh HL, Tsai SJ. Lithium May Be Useful in the Prevention of Alzheimer's Disease in Individuals at Risk of Presenile Familial Alzheimer's Disease. Med Hypotheses. 2008;71(6):948-51. PubMed PMID: 18760542.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lithium may be useful in the prevention of Alzheimer's disease in individuals at risk of presenile familial Alzheimer's disease. AU - Yeh,Heng-Liang, AU - Tsai,Shih-Jen, Y1 - 2008/08/28/ PY - 2008/03/03/received PY - 2008/03/03/revised PY - 2008/03/03/accepted PY - 2008/9/2/pubmed PY - 2009/2/20/medline PY - 2008/9/2/entrez SP - 948 EP - 51 JF - Medical hypotheses JO - Med Hypotheses VL - 71 IS - 6 N2 - Alzheimer's disease (AD) is the most common form of dementia among older people. Presenile familial AD (FAD) and sporadic Alzheimer's disease (SAD) have identical brain lesions, containing senile plaques with beta-amyloid (Abeta) peptide and neurofibrillary tangles formed by hyperphosphorylation of a microtubule-associated protein known as tau. However, FAD and SAD differ in onset and genetic transmission. Unlike SAD, presenile FAD is transmitted as a pure autosomal dominant trait. The authors suggest that lithium could be used for AD prevention, particularly in individuals at risk of presenile FAD, which has early onset. Evidence supporting this hypothesis suggests that lithium decreases Abeta peptide production and inhibits the activity of glycogen synthase kinase-3 which induces aggregation of tau protein into tangles, and tau hyperphosphorylation. Prevalence of AD is lower in patients with chronic lithium treatment, which also increases brain-derived neurotrophic factor activity, so might prevent onset in patients at risk for AD. Several considerations are suggested for prevention trials: the effect of lithium could be evaluated in young animal models that express presenile FAD mutant genes; the time, dose, duration and monitoring of lithium therapy are considered; early phenotypes could be monitored for treatment effect; and some other agents, like valproic acid, could also be candidates for prevention. SN - 0306-9877 UR - https://www.unboundmedicine.com/medline/citation/18760542/Lithium_may_be_useful_in_the_prevention_of_Alzheimer's_disease_in_individuals_at_risk_of_presenile_familial_Alzheimer's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-9877(08)00338-1 DB - PRIME DP - Unbound Medicine ER -