Specific targeting of tau oligomers in Htau mice prevents cognitive impairment and tau toxicity following injection with brain-derived tau oligomeric seeds

Diana L. Castillo-Carranza, Julia E. Gerson, Urmi Sengupta, Marcos J. Guerrero-Muñoz, Cristian A. Lasagna-Reeves, Rakez Kayed

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Neurodegenerative disease is one of the greatest health crises in the world and as life expectancy rises, the number of people affected will continue to increase. The most common neurodegenerative disease, Alzheimer's disease, is a tauopathy, characterized by the presence of aggregated tau, namely in the form of neurofibrillary tangles. Historically, neurofibrillary tangles have been considered the main tau species of interest in Alzheimer's disease; however, we and others have shown that tau oligomers may be the most toxic form and the species responsible for the spread of pathology. We developed a novel anti-tau oligomer-specific mouse monoclonal antibody (TOMA) and investigated the potential of anti-tau oligomer passive immunization in preventing the toxicity of tau pathology in Htau mice. We injected pure brain-derived tau oligomers intracerebrally in 3-month-old wild-type and Htau mice and investigated the protective effects of a single 60 μg TOMA injection when compared to the same dose of non-specific IgG and found that TOMA conferred protection against the accumulation of tau oligomers and cognitive deficits for up to 1 month after treatment. Additionally, we injected pure brain-derived tau oligomers intracerebrally in 3-month-old wild-type and Htau mice and treated animals with biweekly injections of 60 μg TOMA or non-specific IgG. We found that long-term administration of TOMA was effective as a preventative therapy, inhibiting oligomeric tau and preserving memory function. These results support the critical role of oligomeric tau in disease progression and validate tau oligomers as a potential drug target.

Original languageEnglish (US)
JournalJournal of Alzheimer's Disease
Volume40
Issue numberS1
DOIs
StatePublished - 2014

Fingerprint

Seeds
Injections
Brain
Monoclonal Antibodies
Neurofibrillary Tangles
Neurodegenerative Diseases
Alzheimer Disease
Immunoglobulin G
Tauopathies
Pathology
Passive Immunization
Cognitive Dysfunction
Poisons
Life Expectancy
Disease Progression
Health
Therapeutics
Pharmaceutical Preparations

Keywords

  • Alzheimer's disease
  • immunotherapy
  • propagation
  • seeding
  • tau oligomers
  • tauopathies

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology
  • Medicine(all)

Cite this

Specific targeting of tau oligomers in Htau mice prevents cognitive impairment and tau toxicity following injection with brain-derived tau oligomeric seeds. / Castillo-Carranza, Diana L.; Gerson, Julia E.; Sengupta, Urmi; Guerrero-Muñoz, Marcos J.; Lasagna-Reeves, Cristian A.; Kayed, Rakez.

In: Journal of Alzheimer's Disease, Vol. 40, No. S1, 2014.

Research output: Contribution to journalArticle

Castillo-Carranza, Diana L. ; Gerson, Julia E. ; Sengupta, Urmi ; Guerrero-Muñoz, Marcos J. ; Lasagna-Reeves, Cristian A. ; Kayed, Rakez. / Specific targeting of tau oligomers in Htau mice prevents cognitive impairment and tau toxicity following injection with brain-derived tau oligomeric seeds. In: Journal of Alzheimer's Disease. 2014 ; Vol. 40, No. S1.
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