The "lEARn" (latent early-life associated regulation) model

An epigenetic pathway linking metabolic and cognitive disorders

Debomoy Lahiri, Bryan Maloney

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Diabetes, cardiovascular disease, hypertension, and other disorders have been unified within the metabolic syndrome. Recently, it has been proposed that Alzheimer's disease (AD) and other degenerative, age-related neurological disorders may also be etiologically linked to the metabolic syndrome in a metabolic-cognitive syndrome. We review current evidence in the field for this unification. In addition, we describe how the latent early-life associated regulation (LEARn) model provides specific mechanisms to predict genetic targets for both metabolic disorders, e.g., diabetes, and neurodegenerative disorders, e.g., AD. The LEARn model is based on environmental induction of latent epigenetic misregulation, which develops into disease upon suffering additional environmental insults. We review structural differences between gene sequences that are and are not susceptible to LEARn misregulation. In addition to suggesting research targets such as the IDE and SORCS1 genes, which are implicated in both AD and diabetes, LEARn suggests specific mechanisms for pre-disease remediation, based on nutritional adjustment of aberrant DNA methylation and oxidation. The possibility of a single metabolic-cognitive disorder opens up the possibility of unified preventative treatments that reduce monetary and social costs of disease. LEARn suggests specific, testable pathways within the large theory.

Original languageEnglish
JournalJournal of Alzheimer's Disease
Volume30
Issue numberSUPPL.2
DOIs
StatePublished - 2012

Fingerprint

Metabolic Networks and Pathways
Epigenomics
Alzheimer Disease
Social Adjustment
Cost of Illness
DNA Methylation
Nervous System Diseases
Neurodegenerative Diseases
Genes
Cardiovascular Diseases
Hypertension
Research
Therapeutics

Keywords

  • Epigenetic
  • epigenomic
  • gene regulation
  • idiopathic disease
  • metabolic-cognitive syndrome
  • sporadic disease
  • two-hit

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology

Cite this

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