Cerebrospinal Fluid Amyloid Beta, Tau Levels, Apolipoprotein, and 1H-MRS Brain Metabolites in Alzheimer's Disease: A Systematic Review

Piersson, Albert Dayor; Mohamad, Mazlyfarina; Rajab, Fadilah; Suppiah, Subapriya

doi:10.1016/j.acra.2020.06.006

Cited by 20 publications

(14 citation statements)

References 48 publications

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“…The decline in Cho/Cr ratio in the basal forebrain was observed in 6- and 8-month-old APP/PS1 mice compared with wild type mice of similar age, but we found no changes in the hippocampus. It is well recognized that the decline in the NAA/Cr ratio is a common manifestation of Alzheimer’s disease [ 23 , 46 ]. Our findings support this conclusion as the NAA/Cr ratio in the basal forebrain and hippocampus decreased in APP/PS1 mice.…”

Section: Discussionmentioning

confidence: 99%

Chemical genetic activation of the cholinergic basal forebrain hippocampal circuit rescues memory loss in Alzheimer’s disease

Yang

et al. 2022

Alz Res Therapy

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Background The degeneration of the cholinergic circuit from the basal forebrain to the hippocampus contributes to memory loss in patients suffering from Alzheimer’s disease (AD). However, the internal relationships between the acetylcholine (Ach) cycle and memory decline during the early stages of AD currently remain unknown. Here, we investigate the mechanisms underlying the activation of the cholinergic circuit and its impact on learning and memory using APP/PS1 mice models. Methods Novel object recognition and Morris water maze tests were used to measure learning and memory function. Magnetic resonance spectrum (MRS) imaging was applied to longitudinally track changes in neurochemical metabolism in APP/PS1 mice aged 2, 4, 6, and 8 months. The number of neurons and the deposition of Aβ plaques were measured using Nissl, immunohistochemistry, and Thioflavin S staining. We then employed a chemogenetic strategy to selectively activate the cholinergic circuit from the medial septal nucleus (MS) and the vertical limb of the diagonal band nucleus (VDB) on the basal forebrain to the hippocampus. MRS and immunoblotting techniques were used to measure the neurochemical metabolism levels and cholinergic-related proteins, respectively. Results We found that the levels of choline (Cho) in the basal forebrain were markedly higher compared to other brain regions and that its decrease along with N-acetyl aspartate (NAA) levels in the hippocampus was accompanied by memory deficits in APP/PS1 mice aged 4, 6, and 8 months. In terms of pathology, we observed that the deposition of Aβ plaques gradually aggravated throughout the cerebral cortex and hippocampus in APP/PS1 mice aged 6 and 8 months, while no Aβ deposition was detected in the basal forebrain. In contrast, the activity of choline acetyltransferase (ChAT) enzyme in the basal forebrain was decreased at 6 months of age and the cholinergic neurons were lost in the basal forebrain at 8 months of age. In addition, the activation of the cholinergic circuit from the MS and VDB to the hippocampus using chemical genetics is able to improve learning and reduce memory impairment in APP/PS1 mice. Similarly, the levels of Cho in the basal forebrain; NAA in the hippocampus, as well as the expression of ChAT and vesicular acetylcholine transporter (vAchT) in the basal forebrain; and muscarinic acetylcholine receptor 2 (CHRM2) in the hippocampus all increased. Conclusions These findings demonstrate that the neurochemical Cho and NAA of the cholinergic circuit can be used as biomarkers to enable the early diagnosis of AD. In addition, memory impairment in APP/PS1 mice can be attenuated using chemical genetics-driven Ach cycle activity of the cholinergic circuit.

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Section: Discussionmentioning

confidence: 99%

Chemical genetic activation of the cholinergic basal forebrain hippocampal circuit rescues memory loss in Alzheimer’s disease

Yang

et al. 2022

Alz Res Therapy

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“…A single-voxel in vivo 1 H-MRS data will be obtained using a two-dimensional point-resolved spectroscopic pulse sequence (PRESS), as it is the most commonly used 1 H-MRS technique for the study of AD [ 28 ]. The PRESS acquisition method offers the advantage of yielding 2-fold signal from its spin-echo compared to its counterpart, stimulated echo acquisition mode [ 33 , 34 ].…”

Section: Methodsmentioning

confidence: 99%

Multiparametric MRI for the improved diagnostic accuracy of Alzheimer’s disease and mild cognitive impairment: Research protocol of a case-control study design

et al. 2021

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Background Alzheimer’s disease (AD) is a major neurocognitive disorder identified by memory loss and a significant cognitive decline based on previous level of performance in one or more cognitive domains that interferes in the independence of everyday activities. The accuracy of imaging helps to identify the neuropathological features that differentiate AD from its common precursor, mild cognitive impairment (MCI). Identification of early signs will aid in risk stratification of disease and ensures proper management is instituted to reduce the morbidity and mortality associated with AD. Magnetic resonance imaging (MRI) using structural MRI (sMRI), functional MRI (fMRI), diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (1H-MRS) performed alone is inadequate. Thus, the combination of multiparametric MRI is proposed to increase the accuracy of diagnosing MCI and AD when compared to elderly healthy controls. Methods This protocol describes a non-interventional case control study. The AD and MCI patients and the healthy elderly controls will undergo multi-parametric MRI. The protocol consists of sMRI, fMRI, DTI, and single-voxel proton MRS sequences. An eco-planar imaging (EPI) will be used to perform resting-state fMRI sequence. The structural images will be analysed using Computational Anatomy Toolbox-12, functional images will be analysed using Statistical Parametric Mapping-12, DPABI (Data Processing & Analysis for Brain Imaging), and Conn software, while DTI and 1H-MRS will be analysed using the FSL (FMRIB’s Software Library) and Tarquin respectively. Correlation of the MRI results and the data acquired from the APOE genotyping, neuropsychological evaluations (i.e. Montreal Cognitive Assessment [MoCA], and Mini–Mental State Examination [MMSE] scores) will be performed. The imaging results will also be correlated with the sociodemographic factors. The diagnosis of AD and MCI will be standardized and based on the DSM-5 criteria and the neuropsychological scores. Discussion The combination of sMRI, fMRI, DTI, and MRS sequences can provide information on the anatomical and functional changes in the brain such as regional grey matter volume atrophy, impaired functional connectivity among brain regions, and decreased metabolite levels specifically at the posterior cingulate cortex/precuneus. The combination of multiparametric MRI sequences can be used to stratify the management of MCI and AD patients. Accurate imaging can decide on the frequency of follow-up at memory clinics and select classifiers for machine learning that may aid in the disease identification and prognostication. Reliable and consistent quantification, using standardised protocols, are crucial to establish an optimal diagnostic capability in the early detection of Alzheimer’s disease.

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“…The articles retrieved had to meet the inclusion criteria set forth: (1) human subjects, but healthy (nondemented) and/ or patients with any type of dementia (P; patient population); 2 http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp) for case-control and cohort studies was used to evaluate the risk of bias. This qualitative assessment scale has been widely used in previous systematic reviews (24,32,33). The NOS is based on 3 subcategories: (selection, comparability, and exposure/outcome) with an overall total of 9 indicative of the highest attained methodological quality.…”

Section: Study Selectionmentioning

confidence: 99%

“…The Diagnostic and Statistical Manual of Mental Disorders (DSM–5) (21) acknowledges the contribution of genetic testing for assessing AD genetic risk factor, neuropsychological testing for assessing cognitive domain and the integral role of CSF Aβ and tau, including magnetic resonance imaging (MRI)-detected atrophy in the diagnosis of AD. These biomarkers are also very well recommended in the diagnostic guideline for AD (22,23), given that their combination is posited to improve diagnostic accuracy of early onset of AD and prediction of conversion to the clinical stages of AD (24). However, while systematic reviews have been conducted on CSF Aβ alone (25) or in combination with MRI and positron emission tomography (PET) to evaluate gray matter changes (26), there is less focus on ventricular changes in neurodegeneration, especially in patients with AD.…”

Section: Introductionmentioning

confidence: 99%

Association of MRI-measured cerebral ventricular volume with APOE ε4 genotype, cerebrospinal fluid biomarkers (Aβ42 and Tau) and neuropsychological measures in Alzheimer’s disease: A Systematic Review

Piersson

Mohamad

Rajab

et al. 2020

Preprint

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Rationale and ObjectivesAlthough neuroimaging studies suggest that the cerebral ventricle is independently associated with APOE ε4, cerebrospinal fluid (CSF) biomarkers, and neuropsychological scores in aging and Alzheimer’s disease (AD), there is no formal synthesis of these findings. We summarized the association of ventricular changes with APOE ε4, CSF biomarkers, and neuropsychological measures.Materials and MethodsThe Preferred Reporting Items for Systematic reviews and Meta-Analyses guideline was used. PubMed, Scopus, Ovid, Cochrane, and grey literature were searched, and assessment of eligible articles was conducted using the Newcastle-Ottawa Scale.Results24 studies met the inclusion criteria. Progressive ventricular volume is increased in AD patients at an average volume of 4.4 – 4.7 cm3/ year compared to average volumes of 2.7 – 2.9 cm3/ year and 1.1 – 1.4 cm3/year for patients with MCI and healthy controls (HCs) respectively. The ventricular volume is estimated to increase by 1.7 cm3/year for progression from MCI to AD. APOE ε4 is an independent risk factor for ventricular enlargement in aging and dementia, with AD patients most affected. The combination of CSF Aβ42 with ventricular volume compared to tau is more robust, for tracking the progression of the AD continuum. Further, the combination of ventricular volume with mini-mental state examination (MMSE) scores is the most robust for differentiating AD and MCI from HCs and tracking the progression of the disease.ConclusionThe combination of ventricular volume with APOE ε4, CSF Aβ42, and MMSE scores independently may be potentially useful biomarkers for differentiating and tracking the progression of AD.

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Cerebrospinal Fluid Amyloid Beta, Tau Levels, Apolipoprotein, and 1H-MRS Brain Metabolites in Alzheimer's Disease: A Systematic Review

Cited by 20 publications

References 48 publications

Chemical genetic activation of the cholinergic basal forebrain hippocampal circuit rescues memory loss in Alzheimer’s disease

Chemical genetic activation of the cholinergic basal forebrain hippocampal circuit rescues memory loss in Alzheimer’s disease

Multiparametric MRI for the improved diagnostic accuracy of Alzheimer’s disease and mild cognitive impairment: Research protocol of a case-control study design

Association of MRI-measured cerebral ventricular volume with APOE ε4 genotype, cerebrospinal fluid biomarkers (Aβ42 and Tau) and neuropsychological measures in Alzheimer’s disease: A Systematic Review

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