Thyroid hormones (THs) are essential in normal brain development, and cognitive and emotional functions. THs act through a cascade of events including uptake by the target cells by specific cell membrane transporters, activation or inactivation by deiodinase enzymes, and interaction with nuclear thyroid hormone receptors. Several thyroid responsive genes have been described in the developing and in the adult brain and many studies have demonstrated a systemic or local reduction in TH availability in neurologic disease and after brain injury. In this review, the main factors and mechanisms associated with the THs in the normal and damaged brain will be evaluated in different regions and cellular contexts. Furthermore, the most common animal models used to study the role of THs in brain damage and cognitive impairment will be described and the use of THs as a potential recovery strategy from neuropathological conditions will be evaluated. Finally, particular attention will be given to the link observed between TH alterations and increased risk of Alzheimer’s Disease (AD), the most prevalent neurodegenerative and dementing condition worldwide.

In a healthy brain, neuroinflammation, controlled by the main intermediary for the immune response microglia and astrocytes, contributes to maintain physiological functions such as secretion of neurotrophic factors, removal of cell tau and amyloid-β (Aβ) debris, and local homeostasis. When the immune response becomes chronic, it can become pathological and fuel neuroinflammation, causing glial cells to malfunction and not perform their function of clearing debris, resulting in further damage to neurons. Multiple studies highlight that an intense crosstalk is activated between peripheral blood white cells (PBWCs) and central nervous system (CNS). Nevertheless, how PBWC can be carriers of biomarkers of the CNS neuropathological states it is still far to be completely known. In this work, we aimed to observe how PBWC content could be related to moderate-severity of DAT in order to have early signals from of pathological neurodegeneration brain initiate. Protein analysis have been performed in PBWC of Mild Cognitive Impairment (MCI) and DAT patients in respect to those of healthy controls and differently expressed proteins have been investigated. Our data showed a deregulation of pathways involved in neurodegeneration since from MCI level and deregulated proteins that can be considered markers for DAT onset and progression.

Thyroid hormones (THs) critically regulate metabolism and the central nervous system (CNS) functions, acting as key factors in neuronal differentiation, synaptogenesis and myelination. Furthermore, they play a central role in regulation of cognitive process and behavior. Therefore, compromised TH signaling can interfere with normal brain function and promote neurodegenerative progression and dementia. This review explores the role of THs from embryonic development through adulthood, with particular emphasis on their crucial role in neurogenesis. We discuss key components of TH metabolism and signaling, highlighting their neuroprotective functions in maintaining cellular homeostasis. Furthermore, we address how disruptions in TH signaling contribute to cognitive decline observed in dementia with effects that are even more pronounced in Alzheimer’s Disease (AD).