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

• Published in: Cellular and molecular neurobiology Vol. 43; no. 7; pp. 3405 - 3416
• Main Authors: AlAnazi, Faisal Holil, Al-kuraishy, Hayder M., Alexiou, Athanasios, Papadakis, Marios, Ashour, Mohamed H. Mazhar, Alnaaim, Saud A., Elhussieny, Omnya, Saad, Hebatallah M., Batiha, Gaber El-Saber
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.10.2023; Springer Nature B.V
• Subjects: Alzheimer's disease; Autophagy; Biomedical and Life Sciences; Biomedicine; Brain-derived neurotrophic factor; Cell Biology; Developmental plasticity; Hypothyroidism; Metabolism; Neurobiology; Neurodegenerative diseases; Neuropathology; Neurosciences; Oxidative stress; Phosphorylation; Review Paper; Risk factors; Synaptic plasticity; Synaptogenesis; Tau protein; Thyroid hormones; Transthyretin; Oxidative stress; Thyroid-stimulating hormone; Mitochondrial dysfunction; Alzheimer’s disease; Hypothyroidism
• ISSN: 0272-4340; 1573-6830
• DOI: 10.1007/s10571-023-01392-y

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 (A β ) 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 A β 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. Graphical Abstract