Resting-state brain connectivity in healthy young and middle-aged adults at risk of progressive Alzheimer’s disease

Kucikova, Ludmila; Goerdten, Jantje; Dounavi, Maria‐Eleni; Mak, Elijah; Su, Li; Waldman, Adam; Danso, Samuel; Muñiz‐Terrera, Graciela; Ritchie, Craig W.

doi:10.1016/j.neubiorev.2021.07.024

Cited by 23 publications

(27 citation statements)

References 111 publications

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“…Although increased FC of cortical and hippocampal networks has been demonstrated in patients who have amyloid plaques and are at risk for developing AD (6), we show here that cognitively normal individuals show early increases of cingulate BOLD FC, several years before reaching the threshold for amyloid positivity on PET scans. This indicates that increased FC of the cingulate circuitry represents a very early functional symptom of incipient AD.…”

Section: Resultscontrasting

confidence: 50%

“…Neuronal deficits can also lead to alterations of functional connectivity (FC), measured with resting-state functional Magnetic Resonance Imaging (rsfMRI), a translational tool that is used extensively in clinical research. Indeed, increased FC of cortical and hippocampal regions occurs before amyloid plaque deposition in App mouse models (3)(4)(5) and in individuals at risk for AD, such as APOE-ε4 carriers (6). Network activity and FC thus represent clinically relevant readouts for early AD, and defining the mechanisms that underlie these changes can be important for therapeutic development.…”

Section: Main Textmentioning

confidence: 99%

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Astrocyte calcium dysfunction causes early network hyperactivity in Alzheimer’s Disease

Shah

Gsell

Wahis

et al. 2022

Preprint

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Dysfunctions of network activity and functional connectivity (FC) represent early events in Alzheimer’s disease (AD), but the underlying mechanisms remain unclear. Astrocytes regulate neuronal activity in the healthy brain, but their involvement in early network hyperactivity in AD is unknown. We show increased FC in the human cingulate cortex, several years before amyloid deposition. We found the same early cingulate FC disruption and neuronal hyperactivity in AppNL-F mice. Crucially, these network disruptions are accompanied by decreased astrocyte calcium signaling. Recovery of astroglial calcium activity normalizes neuronal hyperactivity and FC, as well as seizure susceptibility and day/night behavioral hyperactivity. In conclusion, we show for the first time that astrocytes mediate initial features of AD and drive clinically relevant phenotypes.

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Section: Resultscontrasting

confidence: 50%

Section: Main Textmentioning

confidence: 99%

Astrocyte calcium dysfunction causes early network hyperactivity in Alzheimer’s Disease

Shah

Gsell

Wahis

et al. 2022

Preprint

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“…Some of these non-coding RNAs have been shown to accumulate within MSC-EVs [ 54 ]. Interestingly, as reported by previous [ 32 ] and recent [ 54 , 55 , 56 ] studies, the preliminary and advanced stages of AD can be easily distinguished. The age of AD patients is critically important for their therapy, as specifically discussed in Section 4 .…”

Section: Role Of the Extracellular Vesicles From Mesenchymal Stem Cells: Recent Views About The Alzheimer’s Diseasesupporting

confidence: 60%

“…In fact, the efforts to reduce Aβ synthesis by blockers of BACE-1, and those with anti-tau and anti-Aβ antibodies, were found unable to reduce the structural devastations induced by the disease in critical areas of the brain. A posteriori, it is not surprising that the drugs, inactive on fully developed disease patients, are effective in healthy persons destined to develop the disease in the future, and in patients at an early stage of the disease, reducing and slowing down their later development of AD [ 33 , 54 , 55 , 56 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, intense studies of many AD patients came out largely unsuccessful, as documented by clinical trial attempts that were either concluded without benefit or discontinued [ 4 , 5 ]. Clear positive effects were observed only in healthy persons destined to develop the disease in the future, and in very early patients [ 3 , 63 ], identified by appropriate markers [ 33 , 54 , 55 , 56 ]. Based on the long-term experience in the field, the investigation of BACE-1 and immune therapies has been pursued up to now.…”

Section: Present Therapies For Alzheimer’s Diseasementioning

confidence: 99%

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News about Therapies of Alzheimer’s Disease: Extracellular Vesicles from Stem Cells Exhibit Advantages Compared to Other Treatments

Meldolesi

2022

Biomedicines

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Upon its discovery, Alzheimer’s, the neurodegenerative disease that affects many millions of patients in the world, remained without an effective therapy. The first drugs, made available near the end of last century, induced some effects, which remained only marginal. More promising effects are now present, induced by two approaches. Blockers of the enzyme BACE-1 induce, in neurons and glial cells, decreased levels of Aβ, the key peptide of the Alzheimer’s disease. If administered at early AD steps, the BACE-1 blockers preclude further development of the disease. However, they have no effect on established, irreversible lesions. The extracellular vesicles secreted by mesenchymal stem cells induce therapy effects analogous, but more convenient, than the effects of their original cells. After their specific fusion to target cells, the action of these vesicles depends on their ensuing release of cargo molecules, such as proteins and many miRNAs, active primarily on the cell cytoplasm. Operationally, these vesicles exhibit numerous advantages: they exclude, by their accurate selection, the heterogeneity of the original cells; exhibit molecular specificity due to their engineering and drug accumulation; and induce effective actions, mediated by variable concentrations of factors and molecules and by activation of signaling cascades. Their strength is reinforced by their combination with various factors and processes. The recent molecular and operations changes, induced especially by the stem cell target cells, result in encouraging and important improvement of the disease. Their further development is expected in the near future.

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Dose response of transcranial near infrared light stimulation on brain functional connectivity and cognition in older adults—A randomized comparison

Joshi,

Sinha,

Bowers

et al. 2023

Journal of Biophotonics

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Abstract‘Photobiomodulation, also called low‐level light therapy, has been reported in animal studies to have an effect on brain activity and cognition. However, studies in humans regarding its effect on cognition and brain functional connectivity, and the required dose threshold for achieving the same have been very limited. We compared the effects of different doses of photobiomodulation (PBM) on cognition and resting state brain functional connectivity in 25 cognitively normal adults aged 55 to 70 years. They were randomized to a single session of the sham group, 'low‐dose' and 'high‐dose' groups receiving NIR light with transcranial fluence of 26 and 52 J/cm2 respectively, and intranasal fluence of 9 and 18 J/cm2 respectively. There was a significant increase in resting state functional connectivity of the left superior frontal gyrus (SFG) with the left planum temporale (PT), p = 0.0016, and with the left inferior frontal gyrus, pars triangularis, p = 0.0235 in the 'high‐dose' group only compared to the 'sham' group. There was also a significant improvement in visual search and processing speed (p = 0.012) in the 'high‐dose' group. Replication of these findings in an adequately powered randomised sham‐controlled study in healthy older adults can pave the way for clinical application of NIRL as a therapeutic modality in patients with Alzheimer's disease.This article is protected by copyright. All rights reserved.

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Resting-state brain connectivity in healthy young and middle-aged adults at risk of progressive Alzheimer’s disease

Cited by 23 publications

References 111 publications

Astrocyte calcium dysfunction causes early network hyperactivity in Alzheimer’s Disease

Astrocyte calcium dysfunction causes early network hyperactivity in Alzheimer’s Disease

News about Therapies of Alzheimer’s Disease: Extracellular Vesicles from Stem Cells Exhibit Advantages Compared to Other Treatments

Dose response of transcranial near infrared light stimulation on brain functional connectivity and cognition in older adults—A randomized comparison

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