Dataset Information

Microglial activation and amyloid deposition in mild cognitive impairment: a PET study.

ABSTRACT:

Background

Activated microglia may play a role in the pathogenesis of Alzheimer disease (AD) as they cluster around beta-amyloid (Abeta) plaques. They are, therefore, a potential therapeutic target in both AD and its prodrome amnestic mild cognitive impairment (MCI).

Objective

To characterize in vivo with (11)C-(R)-PK11195 and (11)C-PIB PET the distribution of microglial activation and amyloid deposition in patients with amnestic MCI.

Methods

Fourteen subjects with MCI had (11)C-(R)-PK11195 and (11)C-PIB PET with psychometric tests.

Results

Seven out of 14 (50%) patients with MCI had increased cortical (11)C-PIB retention (p < 0.001) while 5 out of 13 (38%) subjects with MCI showed increased (11)C-(R)-PK11195 uptake. The MCI subgroup with increased (11)C-PIB retention also showed increased cortical (11)C-(R)-PK11195 binding (p < 0.036) though this increase only remained significant in frontal cortex after a correction for multiple comparisons. There was no correlation between regional levels of (11)C-(R)-PK11195 and (11)C-PIB binding in individual patients with MCI: only three of the five MCI cases with increased (11)C-(R)-PK11195 binding had increased levels of (11)C-PIB retention.

Conclusions

Our findings indicate that, while amyloid deposition and microglial activation can be detected in vivo in around 50% of patients with mild cognitive impairment (MCI), these pathologies can occur independently. The detection of microglial activation in patients with MCI suggests that anti-inflammatory therapies may be relevant to the prevention of AD.

SUBMITTER: Okello A

PROVIDER: S-EPMC2817573 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Microglial activation and amyloid deposition in mild cognitive impairment: a PET study.

Okello A A Edison P P Archer H A HA Turkheimer F E FE Kennedy J J Bullock R R Walker Z Z Kennedy A A Fox N N Rossor M M Brooks D J DJ

Neurology 20090101 1

<h4>Background</h4>Activated microglia may play a role in the pathogenesis of Alzheimer disease (AD) as they cluster around beta-amyloid (Abeta) plaques. They are, therefore, a potential therapeutic target in both AD and its prodrome amnestic mild cognitive impairment (MCI).<h4>Objective</h4>To characterize in vivo with (11)C-(R)-PK11195 and (11)C-PIB PET the distribution of microglial activation and amyloid deposition in patients with amnestic MCI.<h4>Methods</h4>Fourteen subjects with MCI had ...[more]

PMID: 19122031

Similar Datasets

Project description:BackgroundMicroglia are increasingly understood to play an important role in the pathogenesis of Alzheimer's disease. The rs75932628 (p.R47H) TREM2 variant is a well-established risk factor for Alzheimer's disease. TREM2 is a microglial cell surface receptor. In this multi-modal/multi-tracer PET/MRI study we investigated the effect of TREM2 p.R47H carrier status on microglial activation, tau and amyloid deposition, brain structure and cognitive profile.MethodsWe compared TREM2 p.R47H carriers (n = 8; median age = 62.3) and participants with mild cognitive impairment (n = 8; median age = 70.7). Participants underwent two [18F]DPA-714 PET/MRI scans to assess TSPO signal, indicative of microglial activation, before and after receiving the seasonal influenza vaccination, which was used as an immune stimulant. Participants also underwent [18F]florbetapir and [18F]AV1451 PET scans to assess amyloid and tau burden, respectively. Regional tau and TSPO signal were calculated for regions of interest linked to Braak stage. An additional comparison imaging healthy control group (n = 8; median age = 45.5) had a single [18F]DPA-714 PET/MRI. An expanded group of participants underwent neuropsychological testing, to determine if TREM2 status influenced clinical phenotype.ResultsCompared to participants with mild cognitive impairment, TREM2 carriers had lower TSPO signal in Braak II (P = 0.04) and Braak III (P = 0.046) regions, despite having a similar burden of tau and amyloid. There were trends to suggest reduced microglial activation following influenza vaccine in TREM2 carriers. Tau deposition in the Braak VI region was higher in TREM2 carriers (P = 0.04). Furthermore, compared to healthy controls TREM2 carriers had smaller caudate (P = 0.02), total brain (P = 0.049) and white matter volumes (P = 0.02); and neuropsychological assessment revealed worse ADAS-Cog13 (P = 0.03) and Delayed Matching to Sample (P = 0.007) scores.ConclusionsTREM2 p.R47H carriers had reduced levels of microglial activation in brain regions affected early in the Alzheimer's disease course and differences in brain structure and cognition. Changes in microglial response may underlie the increased Alzheimer's disease risk in TREM2 p.R47H carriers. Future therapeutic agents in Alzheimer's disease should aim to enhance protective microglial actions.

Project description:Cognitive impairment indicates disturbed brain physiology which can be due to various mechanisms including Alzheimer's pathology. Combined functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) recordings (EEG-fMRI) can assess the interplay between complementary measures of brain activity and EEG changes to be localized to specific brain regions. We used a two-step approach, where we first examined changes related to a syndrome of mild cognitive impairment irrespective of pathology and then studied the specific impact of amyloid pathology. After detailed clinical and neuropsychological characterization as well as a positron emission tomography (PET) scans with the tracer 11-[C]-Pittsburgh Compound B to estimate cerebral amyloid deposition, 14 subjects with mild cognitive impairment (MCI) (mean age 75.6 SD: 8.9) according to standard criteria and 21 cognitively healthy controls (HCS) (mean age 71.8 SD: 4.2) were assessed with EEG-fMRI. Thalamo-cortical alpha-fMRI signal coupling was only observed in HCS. Additional EEG-fMRI signal coupling differences between HCS and MCI were observed in parts of the default mode network, salience network, fronto-parietal network, and thalamus. Individuals with significant cerebral amyloid deposition (amyloid-positive MCI and HCS combined compared to amyloid-negative HCS) displayed abnormal EEG-fMRI signal coupling in visual, fronto-parietal regions but also in the parahippocampus, brain stem, and cerebellum. This finding was paralleled by stronger absolute fMRI signal in the parahippocampus and weaker absolute fMRI signal in the inferior frontal gyrus in amyloid-positive subjects. We conclude that the thalamocortical coupling in the alpha band in HCS more closely reflects previous findings observed in younger adults, while in MCI there is a clearly aberrant coupling in several networks dominated by an anticorrelation in the posterior cingulate cortex. While these findings may broadly indicate physiological changes in MCI, amyloid pathology was specifically associated with abnormal fMRI signal responses and disrupted coupling between brain oscillations and fMRI signal responses, which especially involve core regions of memory: the hippocampus, para-hippocampus, and lateral prefrontal cortex.

Dataset Information

Microglial activation and amyloid deposition in mild cognitive impairment: a PET study.

Background

Objective

Methods

Results

Conclusions

Publications

Microglial activation and amyloid deposition in mild cognitive impairment: a PET study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets