Signatures for viral infection and inflammation in the proximal olfactory system in familial Alzheimer's disease

Bubak, Andrew N.; Merle, Laetitia; Niemeyer, Christy S.; Baxter, B. Dnate’; Polese, Arianna Gentile; Ramakrishnan, Vijay R.; Gomez, Johana; Madrigal, Lucía; Villegas-Lanau, Andrés; Lopera, Francisco; Macklin, Wendy B.; Frietze, Seth; Nagel, Maria A.; Restrepo, Diego

doi:10.1016/j.neurobiolaging.2022.12.004

Cited by 6 publications

(11 citation statements)

References 31 publications

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“…Despite the small sample size involved, which can be considered a minor limitation in functional neuroimaging studies, this article provides an overview of hippocampal connectivity, a subject which has not to date received the attention it deserves, in the pathophysiology of COVID‐related cognitive impairment. This is especially important in light of recent data showing that COVID and viral infections may represent a critical risk factor for the development of AD 4 . In conclusion, this study not only highlights the importance of the hippocampus as a core structure within key cognitive networks, in terms of cognitive impairment in COVID patients, but also suggests that viral infections may constitute a critical risk factor for the development of AD through subtle hippocampal connectivity changes without visible morphological evidence.…”

Section: Discussionsupporting

confidence: 63%

“…This is especially important in light of recent data showing that COVID and viral infections may represent a critical risk factor for the development of AD. 4 In conclusion, this study not only highlights the importance of the hippocampus as a core structure within key cognitive networks, in terms of cognitive impairment in COVID patients, but also suggests that viral infections may constitute a critical risk factor for the development of AD through subtle hippocampal connectivity changes without visible morphological evidence.…”

Section: Vbm Resultsmentioning

confidence: 57%

“…Despite the World Health Organization's declaration that COVID‐19 no longer represents a public emergency, various studies indicate that individuals infected with the virus may experience long‐term adverse health effects over the course of time 1–3 . This is of the utmost importance given the possible risk of COVID‐related dementia, which has been previously postulated in relation to other viral infections 4 . Limited information is currently available concerning cognitive dysfunctions in individuals who recovered from mild COVID‐19 infections and did not require hospitalization, despite the well‐known cognitive manifestations seen in severe COVID infections 1,3,5 …”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3] This is of the utmost importance given the possible risk of COVID-related dementia, which has been previously postulated in relation to other viral infections. 4 Limited information is currently available concerning cognitive dysfunctions in individuals who recovered from mild COVID-19 infections and did not require hospitalization, despite the well-known cognitive manifestations seen in severe COVID infections. 1,3,5 Current existing evidence updated by WHO suggest that post-COVID cognitive syndrome (PCCS) is defined 4 as a condition that "occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis.…”

Section: Introductionmentioning

confidence: 99%

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Infection with COVID‐19 is no longer a public emergency: But what about degenerative dementia?

Yulug,

Ayyıldız,

Ayyıldız

et al. 2023

Journal of Medical Virology

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Although no longer considered a public health threat, post‐COVID cognitive syndrome continues to impact on a considerable proportion of individuals who were infected with COVID‐19. Recent studies have also suggested that COVID may be represent a critical risk factor for the development of Alzheimer's disease (AD). We compared 17 COVID patients with 20 controls and evaluated the effects of COVID‐19 on general cognitive performance, hippocampal volume, and connections using structural and seed‐based connectivity analysis. We showed that COVID patients exhibited considerably worse cognitive functioning and increased hippocampal connectivity supported by the strong correlation between hippocampal connectivity and cognitive scores. Our findings of higher hippocampal connectivity with no observable hippocampal morphological changes even in mild COVID cases may be represent evidence of a prestructural compensatory mechanism for stimulating additional neuronal resources to combat cognitive dysfunction as recently shown for the prodromal stages of degenerative cognitive disorders. Our findings may be also important in light of recent data showing that other viral infections as well as COVID may constitute a critical risk factor for the development of AD. To our knowledge, this is the first study that investigated network differences in COVID patients, with a particular focus on compensatory hippocampal connectivity.

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Section: Discussionsupporting

confidence: 63%

Section: Vbm Resultsmentioning

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Infection with COVID‐19 is no longer a public emergency: But what about degenerative dementia?

Yulug,

Ayyıldız,

Ayyıldız

et al. 2023

Journal of Medical Virology

View full text Add to dashboard Cite

show abstract

“…It has also been postulated that the APP machinery in the olfactory epithelium differs from other parts of the brain. This is because accumulation of Aβ*56 has been found in the olfactory epithelium before transgenic mice show cognitive deficits 75 . Ectopic olfactory receptors, which are expressed in tissues other than the olfactory epithelium, have been frequently reported in recent years, and it is possible that they have functions other than those related to smell 62 .…”

Section: Discussionmentioning

confidence: 99%

Genetic modifiers of cognitive decline in PSEN1 E280A Alzheimer's disease

Sepulveda‐Falla,

Vélez,

Acosta‐Baena

et al. 2024

Alzheimer's & Dementia

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INTRODUCTIONRate of cognitive decline (RCD) in Alzheimer's disease (AD) determines the degree of impairment for patients and of burden for caretakers. We studied the association of RCD with genetic variants in AD.METHODSRCD was evaluated in 62 familial AD (FAD) and 53 sporadic AD (SAD) cases, and analyzed by whole‐exome sequencing for association with common exonic functional variants. Findings were validated in post mortem brain tissue.RESULTSOne hundred seventy‐two gene variants in FAD, and 227 gene variants in SAD associated with RCD. In FAD, performance decline of the immediate recall of the Rey‐Osterrieth figure test associated with 122 genetic variants. Olfactory receptor OR51B6 showed the highest number of associated variants. Its expression was detected in temporal cortex neurons.DISCUSSIONImpaired olfactory function has been associated with cognitive impairment in AD. Genetic variants in these or other genes could help to identify risk of faster memory decline in FAD and SAD patients.

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Deleting the mitochondrial respiration negative regulator MCJ enhances the efficacy of CD8+ T cell adoptive therapies in pre-clinical studies

Wu,

Valenca-Pereira,

Cendali

et al. 2024

Nat Commun

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Mitochondrial respiration is essential for the survival and function of T cells used in adoptive cellular therapies. However, strategies that specifically enhance mitochondrial respiration to promote T cell function remain limited. Here, we investigate methylation-controlled J protein (MCJ), an endogenous negative regulator of mitochondrial complex I expressed in CD8 cells, as a target for improving the efficacy of adoptive T cell therapies. We demonstrate that MCJ inhibits mitochondrial respiration in murine CD8+ CAR-T cells and that deletion of MCJ increases their in vitro and in vivo efficacy against murine B cell leukaemia. Similarly, MCJ deletion in ovalbumin (OVA)-specific CD8+ T cells also increases their efficacy against established OVA-expressing melanoma tumors in vivo. Furthermore, we show for the first time that MCJ is expressed in human CD8 cells and that the level of MCJ expression correlates with the functional activity of CD8+ CAR-T cells. Silencing MCJ expression in human CD8 CAR-T cells increases their mitochondrial metabolism and enhances their anti-tumor activity. Thus, targeting MCJ may represent a potential therapeutic strategy to increase mitochondrial metabolism and improve the efficacy of adoptive T cell therapies.

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Signatures for viral infection and inflammation in the proximal olfactory system in familial Alzheimer's disease

Cited by 6 publications

References 31 publications

Infection with COVID‐19 is no longer a public emergency: But what about degenerative dementia?

Infection with COVID‐19 is no longer a public emergency: But what about degenerative dementia?

Genetic modifiers of cognitive decline in PSEN1 E280A Alzheimer's disease

Deleting the mitochondrial respiration negative regulator MCJ enhances the efficacy of CD8+ T cell adoptive therapies in pre-clinical studies

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