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Lithium reduces tau phosphorylation but not A beta or working memory deficits in a transgenic model with both plaques and tangles.
Am J Pathol. 2007 May; 170(5):1669-75.AJ

Abstract

Glycogen synthase kinase 3 (GSK-3) is a major kinase implicated in the pathogenesis of Alzheimer's disease (AD), and reducing its activity may have therapeutic efficacy. Two variants exist, referred to as GSK-3 alpha and GSK-3beta. In addition to the latter's well-described role in the phosphorylation of tau, reports also suggest that GSK-3 alpha may regulate amyloid precursor protein processing and Abeta formation. The activities of both GSK-3 alpha and GSK-3beta are reduced by lithium, a well-tolerated drug used in humans to combat bipolar disorder. Here, we investigate the therapeutic efficacy of chronic lithium administration in aged 3xTg-AD mice that harbor both plaques and tangles. We found that lithium reduced tau phosphorylation but did not significantly alter the A beta load. Despite the reduction in phosphotau, lithium treatment did not improve deficits in working memory. Although other studies have investigated the effects of lithium on tau biochemistry, this study represents the first to address comprehensively its therapeutic potential on other critical aspects of AD including its effect on A beta and learning and memory. It remains to be determined from human clinical trials whether lithium treatment alone will improve the clinical outcome in AD patients. These results, however, suggest that the most efficacious treatment will be combining lithium with other anti-A beta interventions.

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Authors+Show Affiliations

Caccamo A
Department of Neurobiology and Behavior, University of California, Irvine, 1109 Gillespie Neuroscience Bldg., Irvine, CA 92697-4545, USA.
Oddo S
No affiliation info available
Tran LX
No affiliation info available
LaFerla FM
No affiliation info available

MeSH

Alzheimer DiseaseAmyloid beta-PeptidesAnimalsBlotting, WesternBrainDisease Models, AnimalEnzyme-Linked Immunosorbent AssayFemaleImmunohistochemistryLithium CompoundsMaleMaze LearningMemoryMiceMice, TransgenicNeurofibrillary TanglesPhosphorylationPlaque, Amyloidtau Proteins

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17456772

Citation

Caccamo, Antonella, et al. "Lithium Reduces Tau Phosphorylation but Not a Beta or Working Memory Deficits in a Transgenic Model With Both Plaques and Tangles." The American Journal of Pathology, vol. 170, no. 5, 2007, pp. 1669-75.
Caccamo A, Oddo S, Tran LX, et al. Lithium reduces tau phosphorylation but not A beta or working memory deficits in a transgenic model with both plaques and tangles. Am J Pathol. 2007;170(5):1669-75.
Caccamo, A., Oddo, S., Tran, L. X., & LaFerla, F. M. (2007). Lithium reduces tau phosphorylation but not A beta or working memory deficits in a transgenic model with both plaques and tangles. The American Journal of Pathology, 170(5), 1669-75.
Caccamo A, et al. Lithium Reduces Tau Phosphorylation but Not a Beta or Working Memory Deficits in a Transgenic Model With Both Plaques and Tangles. Am J Pathol. 2007;170(5):1669-75. PubMed PMID: 17456772.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lithium reduces tau phosphorylation but not A beta or working memory deficits in a transgenic model with both plaques and tangles. AU - Caccamo,Antonella, AU - Oddo,Salvatore, AU - Tran,Lana X, AU - LaFerla,Frank M, PY - 2007/4/26/pubmed PY - 2007/6/27/medline PY - 2007/4/26/entrez SP - 1669 EP - 75 JF - The American journal of pathology JO - Am J Pathol VL - 170 IS - 5 N2 - Glycogen synthase kinase 3 (GSK-3) is a major kinase implicated in the pathogenesis of Alzheimer's disease (AD), and reducing its activity may have therapeutic efficacy. Two variants exist, referred to as GSK-3 alpha and GSK-3beta. In addition to the latter's well-described role in the phosphorylation of tau, reports also suggest that GSK-3 alpha may regulate amyloid precursor protein processing and Abeta formation. The activities of both GSK-3 alpha and GSK-3beta are reduced by lithium, a well-tolerated drug used in humans to combat bipolar disorder. Here, we investigate the therapeutic efficacy of chronic lithium administration in aged 3xTg-AD mice that harbor both plaques and tangles. We found that lithium reduced tau phosphorylation but did not significantly alter the A beta load. Despite the reduction in phosphotau, lithium treatment did not improve deficits in working memory. Although other studies have investigated the effects of lithium on tau biochemistry, this study represents the first to address comprehensively its therapeutic potential on other critical aspects of AD including its effect on A beta and learning and memory. It remains to be determined from human clinical trials whether lithium treatment alone will improve the clinical outcome in AD patients. These results, however, suggest that the most efficacious treatment will be combining lithium with other anti-A beta interventions. SN - 0002-9440 UR - https://www.unboundmedicine.com/medline/citation/17456772/Lithium_reduces_tau_phosphorylation_but_not_A_beta_or_working_memory_deficits_in_a_transgenic_model_with_both_plaques_and_tangles_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-9440(10)61379-X DB - PRIME DP - Unbound Medicine ER -