scholarly journals Relationship between Cerebrospinal Fluid Matrix Metalloproteinases Levels and Brain Amyloid Deposition in Mild Cognitive Impairment

Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1496
Author(s):  
Yuuki Sasaki ◽  
Noriyuki Kimura ◽  
Yasuhiro Aso ◽  
Kenichi Yabuuchi ◽  
Miki Aikawa ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Amyloid Deposition ◽  
Emission Tomography ◽  
Cingulate Gyrus ◽  
Posterior Cingulate Gyrus ◽  
Positron Emission ◽  
Csf Levels ◽  
Brain Amyloid Deposition

This study aimed to explore whether cerebrospinal fluid (CSF) levels of matrix metalloproteinases (MMPs), and their inhibitors (TIMPs) were associated with brain amyloid deposition, cortical glucose metabolism, and white matter lesions (WMLs) in individuals with amnestic mild cognitive impairment (MCI). A total of 33 individuals with amnestic MCI (mean age, 75.6 years) underwent 11C-Pittsburgh compound B positron emission tomography (PiB-PET), 18F-fluorodeoxyglucose positron emission tomography, magnetic resonance imaging or computed tomography, and CSF analysis. PET uptake of the frontal and temporoparietal lobes and posterior cingulate gyrus was assessed using the cerebellar cortex as the reference region. WMLs were assessed by the Fazekas scale. CSF levels of MMPs and TIMPs were measured with bead-based multiplex assays. After adjusting for covariates, multiple linear regression analysis showed that CSF levels of MMP-2 were negatively correlated with global PiB uptake (p = 0.035), especially in the parietotemporal lobe and posterior cingulate gyrus (p = 0.016 and p = 0.041, respectively). Moreover, CSF levels of MMP-7 were positively correlated with the severity of WMLs (p = 0.033). CSF levels of MMP-2 and MMP-7 are associated with brain amyloid deposition and severity of WMLs, respectively. These findings provide valuable insights into the role of MMPs in amyloid β catabolism and blood–brain barrier integration at the MCI stage.

scholarly journals Association of weight change with cerebrospinal fluid biomarkers and amyloid positron emission tomography in preclinical Alzheimer’s disease

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Oriol Grau-Rivera ◽  
◽  
Irene Navalpotro-Gomez ◽  
Gonzalo Sánchez-Benavides ◽  
Marc Suárez-Calvet ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Weight Loss ◽  
Cerebrospinal Fluid ◽  
Weight Change ◽  
Emission Tomography ◽  
Link Type ◽  
Preclinical Ad ◽  
Positron Emission ◽  
T Tau

Abstract Background Recognizing clinical manifestations heralding the development of Alzheimer’s disease (AD)-related cognitive impairment could improve the identification of individuals at higher risk of AD who may benefit from potential prevention strategies targeting preclinical population. We aim to characterize the association of body weight change with cognitive changes and AD biomarkers in cognitively unimpaired middle-aged adults. Methods This prospective cohort study included data from cognitively unimpaired adults from the ALFA study (n = 2743), a research platform focused on preclinical AD. Cognitive and anthropometric data were collected at baseline between April 2013 and November 2014. Between October 2016 and February 2020, 450 participants were visited in the context of the nested ALFA+ study and underwent cerebrospinal fluid (CSF) extraction and acquisition of positron emission tomography images with [18F]flutemetamol (FTM-PET). From these, 408 (90.1%) were included in the present study. We used data from two visits (average interval 4.1 years) to compute rates of change in weight and cognitive performance. We tested associations between these variables and between weight change and categorical and continuous measures of CSF and neuroimaging AD biomarkers obtained at follow-up. We classified participants with CSF data according to the AT (amyloid, tau) system and assessed between-group differences in weight change. Results Weight loss predicted a higher likelihood of positive FTM-PET visual read (OR 1.27, 95% CI 1.00–1.61, p = 0.049), abnormal CSF p-tau levels (OR 1.50, 95% CI 1.19–1.89, p = 0.001), and an A+T+ profile (OR 1.64, 95% CI 1.25–2.20, p = 0.001) and was greater among participants with an A+T+ profile (p < 0.01) at follow-up. Weight change was positively associated with CSF Aβ42/40 ratio (β = 0.099, p = 0.032) and negatively associated with CSF p-tau (β = − 0.141, p = 0.005), t-tau (β = − 0.147 p = 0.004) and neurogranin levels (β = − 0.158, p = 0.002). In stratified analyses, weight loss was significantly associated with higher t-tau, p-tau, neurofilament light, and neurogranin, as well as faster cognitive decline in A+ participants only. Conclusions Weight loss predicts AD CSF and PET biomarker results and may occur downstream to amyloid-β accumulation in preclinical AD, paralleling cognitive decline. Accordingly, it should be considered as an indicator of increased risk of AD-related cognitive impairment. Trial registration NCT01835717, NCT02485730, NCT02685969.

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