Primary Hypothyroidism and Alzheimer's Disease: A Tale of Two

Cell Mol Neurobiol. 2023 Oct;43(7):3405-3416. doi: 10.1007/s10571-023-01392-y. Epub 2023 Aug 4.


Hypothyroidism (HPT) HPT could be a risk factor for the development and progression of Alzheimer's disease (AD). In addition, progressive neurodegeneration in AD may affect the metabolism of thyroid hormones (THs) in the brain causing local brain HPT. Hence, the present review aimed to clarify the potential association between HPT and AD. HPT promotes the progression of AD by inducing the production of amyloid beta (Aβ) and tau protein phosphorylation with the development of synaptic plasticity and memory dysfunction. Besides, the metabolism of THs is dysregulated in AD due to the accumulation of Aβ and tau protein phosphorylation leading to local brain HPT. Additionally, HPT can affect AD neuropathology through various mechanistic pathways including dysregulation of transthyretin, oxidative stress, ER stress, autophagy dysfunction mitochondrial dysfunction, and inhibition of brain-derived neurotrophic factor. Taken together there is a potential link between HPT and AD, as HPT adversely impacts AD neuropathology and the reverse is also true.

Keywords: Alzheimer’s disease; Hypothyroidism; Mitochondrial dysfunction; Oxidative stress; Thyroid-stimulating hormone.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease* / metabolism
  • Amyloid beta-Peptides / metabolism
  • Brain / metabolism
  • Humans
  • Hypothyroidism* / complications
  • Hypothyroidism* / metabolism
  • Hypothyroidism* / pathology
  • tau Proteins / metabolism


  • tau Proteins
  • Amyloid beta-Peptides