Association between Thyroid Hormones, Apolipoprotein E, and Cognitive Function among Cognitively-Normal Elderly Dwellers

Kim, Beom-Jun; Moon, Seok Woo

doi:10.30773/pi.2020.0182

Cited by 4 publications

(3 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A diagnosis of hypothyroidism appeared to occur, on average, more than a decade prior to a diagnosis of AD (as defined as the difference between the age of AD onset and age of hypothyroidism onset), irrespective of age of AD onset. Alterations in thyroid function have been associated with a higher risk of developing AD later in life in the neurotypical population [ 33 ], suggesting that complex interactions between thyroid hormone, thyroid function and risk for AD may be particularly salient in the DS population.…”

Section: Discussionmentioning

confidence: 99%

Association between Hypothyroidism Onset and Alzheimer Disease Onset in Adults with Down Syndrome

et al. 2021

View full text Add to dashboard Cite

Adults with Down syndrome (DS) have an exceptionally high frequency of Alzheimer disease (AD) with a wide variability in onset, from 40 to 70 years of age. Equally prevalent in DS is hypothyroidism. In this study, we sought to quantify the relationship between the two. A total of 232 adults with DS and AD were stratified into three AD onset age groups: early (<47 years), typical (48–59), and late (>59). Among patients with available data, differences in the distributions of demographics, hypothyroidism variables (presence, age of onset), thyroid function tests, thyroid autoantibodies, and APOE genotypes were assessed (e.g., chi-squared, Mann–Whitney tests). Spearman and partial Spearman correlations and ordinal logistic regression models were constructed to quantify the association between ages of AD and hypothyroidism onset with and without covariate adjustments. We observed a positive association between the ages of AD and hypothyroidism onset after accounting for APOE-Ɛ4 (correlation: 0.44, 0.24, 0.60; odds ratio: 1.09, 1.05–1.14). However, an early age of hypothyroidism onset and the presence of the APOE-Ɛ4 allele were independently associated with the early age of AD onset. Similar findings were observed when accounting for other factors. Our study provides evidence for the importance of hypothyroidism and associated pathological mechanisms for risk of AD in DS.

show abstract

Section: Discussionmentioning

confidence: 99%

Association between Hypothyroidism Onset and Alzheimer Disease Onset in Adults with Down Syndrome

et al. 2021

View full text Add to dashboard Cite

show abstract

“…In postmenopausal women, low cognitive functions are associated with the presence of ApoE4 allele and lower levels of FT3 and TT3, although thyroid-stimulating hormone (TSH) levels are increased [ 24 ]. Lower serum TSH levels in combination with ApoE4 allele were shown to impair memory and cognitive performance of elder Koreans [ 25 ]. We studied 60 carriers of ApoE4 allele including 32 male and 28 female subjects, with the gender ratio 1.14.…”

Section: Discussionmentioning

confidence: 99%

Ageing related thyroid deficiency increases brain-targeted transport of liver-derived ApoE4-laden exosomes leading to cognitive impairment

et al. 2022

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is the prevalent cause of dementia in the ageing world population. Apolipoprotein E4 (ApoE4) allele is the key genetic risk factor for AD, although the mechanisms linking ApoE4 with neurocognitive impairments and aberrant metabolism remains to be fully characterised. We discovered a significant increase in the ApoE4 content of serum exosomes in old healthy subjects and AD patients carrying ApoE4 allele as compared with healthy adults. Elevated exosomal ApoE4 demonstrated significant inverse correlation with serum level of thyroid hormones and cognitive function. We analysed effects of ApoE4-containing peripheral exosomes on neural cells and neurological outputs in aged or thyroidectomised young mice. Ageing-associated hypothyroidism as well as acute thyroidectomy augmented transport of liver-derived ApoE4 reach exosomes into the brain, where ApoE4 activated nucleotide-binding oligomerisation domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome by increasing cholesterol level in neural cells. This, in turn, affected cognition, locomotion and mood. Our study reveals pathological potential of exosomes-mediated relocation of ApoE4 from the periphery to the brain, this process can represent potential therapeutic target.

show abstract

“…In postmenopausal women, low cognitive functions are associated with the presence of ApoE4 allele and lower levels of FT3 and TT3, although thyroid-stimulating hormone (TSH) levels are increased 19 . Lower serum TSH levels and ApoE4 allele in uence with memory cognitive functions of elder Koreans 20 . We studied 60 carriers of ApoE4 allele including 32 male and 28 female subjects, the related gender ratio was 1.14.…”

Section: Liver-derived Apoe4 Causes Neurological Impairmentsmentioning

confidence: 99%

Ageing related thyroid deficiency increases brain-targeted transport of liver-derived ApoE4-laden exosomes leading to cognitive impairments

Zhang

Gong

Chen

et al. 2021

Preprint

View full text Add to dashboard Cite

Alzheimer's disease (AD) is the prevalent cause of dementia in the ageing world population. Apolipoprotein E4 (ApoE4) allele is the key genetic risk factor for AD, although the mechanisms linking APOE4 with neurocognitive impairments and aberrant metabolism remains to be fully characterised. We discovered significantly increase in the ApoE4 contents of serum exosomes in old healthy subjects and AD patients carrying ApoE4 allele as compared with adult healthy subjects. Elevated exosomal ApoE4 demonstrated significant inverse correlation with serum thyroid hormones level and cognitive function. We analysed effects of ApoE4 in peripheral exosomes on the neurological disorders in aged or thyroidectomied young mice. Ageing-associated hypothyroidism as well as acute thyreoidectomy augmented transport of liver-derived ApoE4 reach exosomes into the brain, where ApoE4 activates NLRP3 inflammasome by increasing cholesterol level in neural cells. This, in turn, affects cognition, locomotion and mood. Our study reveals pathological potential of exosomes-mediated relocation of ApoE4 from the periphery to the brain, which process can represent potential therapeutic target.

show abstract

Association between Thyroid Hormones, Apolipoprotein E, and Cognitive Function among Cognitively-Normal Elderly Dwellers

Cited by 4 publications

References 43 publications

Association between Hypothyroidism Onset and Alzheimer Disease Onset in Adults with Down Syndrome

Association between Hypothyroidism Onset and Alzheimer Disease Onset in Adults with Down Syndrome

Ageing related thyroid deficiency increases brain-targeted transport of liver-derived ApoE4-laden exosomes leading to cognitive impairment

Ageing related thyroid deficiency increases brain-targeted transport of liver-derived ApoE4-laden exosomes leading to cognitive impairments

Contact Info

Product

Resources

About