Neuroinflammation and functional connectivity in Alzheimer’s disease: interactive influences on cognitive performance
| Autor: | P.S. Jones, James B. Rowe, William Richard Bevan-Jones, Kamen A. Tsvetanov, John T. O'Brien, Elijah Mak, Li Su, Robin J Borchert, Robert Arnold, Luca Passamonti |
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| Přispěvatelé: | Passamonti, L [0000-0002-7937-0615], Tsvetanov, KA [0000-0002-3178-6363], Rowe, JB [0000-0001-7216-8679], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Hippocampus neuroinflammation 0302 clinical medicine Cognition Medicine Research Articles Temporal cortex Aged 80 and over Cerebral Cortex 0303 health sciences Alzheimer's disease PET [11C]PK11195 functional connectivity independent component analysis medicine.diagnostic_test General Neuroscience Middle Aged Magnetic Resonance Imaging Disease Progression Biomarker (medicine) Female Microglia medicine.symptom 03 medical and health sciences Alzheimer Disease Neurobiology of Disease Connectome Dementia Humans Effects of sleep deprivation on cognitive performance Cognitive deficit Neuroinflammation 030304 developmental biology Aged Inflammation Amyloid beta-Peptides business.industry medicine.disease Isoquinolines Amides 030104 developmental biology Positron-Emission Tomography Radiopharmaceuticals business Functional magnetic resonance imaging Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | The journal of neuroscience (Online) 39 (2019): 7218–7226. doi:10.1523/JNEUROSCI.2574-18.2019 info:cnr-pdr/source/autori:Passamonti L.; Tsvetanov K.A.; Jones P.S.; Bevan-Jones W.R.; Arnold R.; Borchert R.J.; Mak E.; Su L.; O'Brien J.T.; Rowe J.B./titolo:Neuroinflammation and Functional Connectivity in Alzheimer's Disease: Interactive Influences on Cognitive Performance/doi:10.1523%2FJNEUROSCI.2574-18.2019/rivista:The journal of neuroscience (Online)/anno:2019/pagina_da:7218/pagina_a:7226/intervallo_pagine:7218–7226/volume:39 The Journal of Neuroscience |
| DOI: | 10.1101/532291 |
| Popis: | Neuroinflammation is a key part of the etio-pathogenesis of Alzheimer’s disease. We test the relationship between neuroinflammation and the disruption of functional connectivity in large-scale networks, and their joint influence on cognitive impairment.We combined [11C]PK11195 positron emission tomography (PET) and resting-state functional magnetic resonance imaging (rs-fMRI) in 28 humans (13 females/15 males) with clinical diagnosis of probable Alzheimer’s disease or mild cognitive impairment with positive PET biomarker for amyloid, and 14 age-, sex-, and education-matched healthy humans (8 females/6 males). Source-based ‘inflammetry’ was used to extract principal components of [11C]PK11195 PET signal variance across all participants. rs-fMRI data were pre-processed via independent component analyses to classify neuronal and non-neuronal signals. Multiple linear regression models identified sources of signal co-variance between neuroinflammation and brain connectivity profiles, in relation to group and cognitive status.Patients showed significantly higher [11C]PK11195 binding relative to controls, in a distributed spatial pattern including the hippocampus, medial, and inferior temporal cortex. Patients with enhanced loading on this [11C]PK11195 binding distribution displayed diffuse abnormal functional connectivity. The expression of a stronger association between such abnormal connectivity and higher levels of neuroinflammation correlated with worse cognitive deficits.Our study suggests that neuroinflammation relates to the pathophysiological changes in network function that underlie cognitive deficits in Alzheimer’s disease. Neuroinflammation, and its association with functionally-relevant reorganisation of brain networks, is proposed as a target for emerging immuno-therapeutic strategies aimed at preventing or slowing the emergence of dementia.Significance StatementNeuroinflammation is an important aspect of Alzheimer’s disease (AD), but it was not known whether the influence of neuroinflammation on brain network function in humans was important for cognitive deficit.Our study provides clear evidence that in vivo neuroinflammation in AD impairs large-scale network connectivity; and that the link between inflammation and functional network connectivity is relevant to cognitive impairment.We suggest that future studies should address how neuroinflammation relates to network function as AD progresses; and whether the neuroinflammation in AD is reversible, as the basis of immunotherapeutic strategies to slow the progression of AD. |
| Databáze: | OpenAIRE |
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