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- Johansson, Annica, 1969, et al.
(författare)
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Increased frequency of a new polymorphism in the cell division cycle 2 (cdc2) gene in patients with Alzheimer's disease and frontotemporal dementia.
- 2003
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Ingår i: Neuroscience letters. - : Elsevier BV. - 0304-3940. ; 340:1, s. 69-73
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies show linkage between Alzheimer's disease (AD) and two loci on chromosome 10. The cell division cycle 2 (cdc2) gene is located close to one of the chromosome 10 markers, and is a candidate gene for AD since it is involved in the pathogenesis of AD. We sequenced coding exons and flanking intronic sequences and the promoter region on the cdc2 gene and found three new single nucleotide polymorphisms (SNPs). We analyzed 272 Caucasian AD cases, 160 controls and 70 cases with frontotemporal dementia (FTD) for these SNPs. Homozygosity for one of the SNPs (Ex6+7I/D) was more frequent in both AD and FTD cases than in controls. In the combined tauopathy (AD and FTD) group the odds ratio (OR) was 1.77 (95% CI 1.19-2.63) for the Ex6+7II genotype. Our findings suggest that the Ex6+7I allele is associated with tauopathies, both AD and FTD.
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| 3. |
- Cedres, N., et al.
(författare)
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Association of Cerebrovascular and Alzheimer Disease Biomarkers With Cholinergic White Matter Degeneration in Cognitively Unimpaired Individuals
- 2022
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 99:15
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives Several pathologic processes might contribute to the degeneration of the cholinergic system in aging. We aimed to determine the contribution of amyloid, tau, and cerebrovascular biomarkers toward the degeneration of cholinergic white matter (WM) projections in cognitively unimpaired individuals. Methods The contribution of amyloid and tau pathology was assessed through CSF levels of the A beta(42/40) ratio and phosphorylated tau (p-tau). CSF A beta(38) levels were also measured. Cerebrovascular pathology was assessed using automatic segmentations of WM lesions (WMLs) on MRI. Cholinergic WM projections (i.e., cingulum and external capsule pathways) were modeled using tractography based on diffusion tensor imaging data. Sex and APOE epsilon 4 carriership were also included in the analysis as variables of interest. Results We included 203 cognitively unimpaired individuals from the H70 Gothenburg Birth Cohort Studies (all individuals aged 70 years, 51% female). WM lesion burden was the most important contributor to the degeneration of both cholinergic pathways (increase in mean square error [IncMSE] = 98.8% in the external capsule pathway and IncMSE = 93.3% in the cingulum pathway). Levels of A beta(38) and p-tau also contributed to cholinergic WM degeneration, especially in the external capsule pathway (IncMSE = 28.4% and IncMSE = 23.4%, respectively). The A beta(42/40) ratio did not contribute notably to the models (IncMSE<3.0%). APOE epsilon 4 carriers showed poorer integrity in the cingulum pathway (IncMSE = 21.33%). Women showed poorer integrity of the external capsule pathway (IncMSE = 21.55%), which was independent of amyloid status as reflected by the nonsignificant differences in integrity when comparing amyloid-positive vs amyloid-negative women participants (T-201 = -1.55; p = 0.123). Discussion In cognitively unimpaired older individuals, WMLs play a central role in the degeneration of cholinergic pathways. Our findings highlight the importance of WM lesion burden in the elderly population, which should be considered in the development of prevention programs for neurodegeneration and cognitive impairment.
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| 4. |
- Voevodskaya, O., et al.
(författare)
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Brain myoinositol as a potential marker of amyloid-related pathology: A longitudinal study
- 2019
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 92:5
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo investigate the association between longitudinal changes in proton magnetic resonance spectroscopy (MRS) metabolites and amyloid pathology in individuals without dementia, and to explore the relationship between MRS and cognitive decline.MethodsIn this longitudinal multiple time point study (a subset of the Swedish BioFINDER), we included cognitively healthy participants, individuals with subjective cognitive decline, and individuals with mild cognitive impairment. MRS was acquired serially in 294 participants (670 individual spectra) from the posterior cingulate/precuneus. Using mixed-effects models, we assessed the association between MRS and baseline -amyloid (A), and between MRS and the longitudinal Mini-Mental State Examination, accounting for APOE, age, and sex.ResultsWhile baseline MRS metabolites were similar in A positive (A+) and negative (A-) individuals, in the A+ group, the estimated rate of change was +1.9%/y for myo-inositol (mI)/creatine (Cr) and -2.0%/y for N-acetylaspartate (NAA)/mI. In the A- group, mI/Cr and NAA/mI yearly change was -0.05% and +1.2%; however, this was not significant across time points. The mild cognitive impairment A+ group showed the steepest MRS changes, with an estimated rate of +2.93%/y (p = 0.07) for mI/Cr and -3.55%/y (p < 0.01) for NAA/mI. Furthermore, in the entire cohort, we found that A+ individuals with low baseline NAA/mI had a significantly higher rate of cognitive decline than A+ individuals with high baseline NAA/mI.ConclusionWe demonstrate that the longitudinal change in mI/Cr and NAA/mI is associated with underlying amyloid pathology. MRS may be a useful noninvasive marker of A-related processes over time. In addition, we show that in A+ individuals, baseline NAA/mI may predict the rate of future cognitive decline.
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| 5. |
- Lindberg, O., et al.
(författare)
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Effects of amyloid pathology and the APOE epsilon 4 allele on the association between cerebrospinal fluid A beta 38 and A beta 40 and brain morphology in cognitively normal 70-years-olds
- 2021
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580. ; 101, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- The association between cerebrospinal fluid (CSF) amyloid beta (A beta) A beta 38 or A beta 40 and brain grey- and white matter integrity is poorly understood. We studied this in 213 cognitively normal 70-year-olds, and in subgroups defined by presence/absence of the APOE epsilon 4 allele and A beta pathology: A beta-/APOE-, A beta+/APOE-, A beta-/APOE+ and A beta+/APOE+. CSF A beta was quantified using ELISA and genotyping for APOE was performed. Low CSF A beta 42 defined A beta plaque pathology. Brain volumes were assessed using Freesurfer-5.3, and white matter integrity using tract-based statistics in FSL. A beta 38 and A beta 40 were positively correlated with cortical thickness, some subcortical volumes and white matter integrity in the total sample, and in 3 of the subgroups: A beta-/APOE-, A beta+/APOE- and A beta-/APOE+. In A beta+/APOE+ subjects, higher A beta 38 and A beta 40 were linked to reduced cortical thickness and subcortical volumes. We hypothesize that production of all A beta species decrease in brain regions with atrophy. In A beta+/APOE+, A beta-dysregulation may be linked to cortical atrophy in which high A beta levels is causing pathological changes in the gray matter of the brain. (C) 2020 The Author(s). Published by Elsevier Inc.
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| 6. |
- Badji, A., et al.
(författare)
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Cerebrospinal Fluid Biomarkers, Brain Structural and Cognitive Performances Between Normotensive and Hypertensive Controlled, Uncontrolled and Untreated 70-Year-Old Adults
- 2022
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hypertension is an important risk factor for Alzheimer's disease (AD). The pathophysiological mechanisms underlying the relationship between AD and hypertension are not fully understood, but they most likely involve microvascular dysfunction and cerebrovascular pathology. Although previous studies have assessed the impact of hypertension on different markers of brain integrity, no study has yet provided a comprehensive comparison of cerebrospinal fluid (CSF) biomarkers and structural brain differences between normotensive and hypertensive groups in a single and large cohort of older adults in relationship to cognitive performances.Objective: The aim of the present work was to investigate the differences in cognitive performances, CSF biomarkers and magnetic resonance imaging (MRI) of brain structure between normotensive, controlled hypertensive, uncontrolled hypertensive, and untreated hypertensive older adults from the Gothenburg H70 Birth Cohort Studies.Methods: As an indicator of vascular brain pathology, we measured white matter hyperintensities (WMHs), lacunes, cerebral microbleeds, enlarged perivascular space (epvs), and fractional anisotropy (FA). To assess markers of AD pathology/neurodegeneration, we measured hippocampal volume, temporal cortical thickness on MRI, and amyloid-beta(42), phosphorylated tau, and neurofilament light protein (NfL) in cerebrospinal fluid. Various neuropsychological tests were used to assess performances in memory, attention/processing speed, executive function, verbal fluency, and visuospatial abilities.Results: We found more white matter pathology in hypertensive compared to normotensive participants, with the highest vascular burden in uncontrolled participants (e.g., lower FA, more WMHs, and epvs). No significant difference was found in any MRI or CSF markers of AD pathology/neurodegeneration when comparing normotensive and hypertensive participants, nor among hypertensive groups. No significant difference was found in most cognitive functions between groups.Conclusion: Our results suggest that good blood pressure control may help prevent cerebrovascular pathology. In addition, hypertension may contribute to cognitive decline through its effect on cerebrovascular pathology rather than AD-related pathology. These findings suggest that hypertension is associated with MRI markers of vascular pathology in the absence of a significant decline in cognitive functions.
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| 7. |
- Srikrishna, Meera, et al.
(författare)
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CT-based volumetric measures obtained through deep learning: Association with biomarkers of neurodegeneration
- 2024
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Ingår i: Alzheimers & Dementia. - 1552-5260. ; 20:1, s. 629-640
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTIONCranial computed tomography (CT) is an affordable and widely available imaging modality that is used to assess structural abnormalities, but not to quantify neurodegeneration. Previously we developed a deep-learning-based model that produced accurate and robust cranial CT tissue classification.MATERIALS AND METHODSWe analyzed 917 CT and 744 magnetic resonance (MR) scans from the Gothenburg H70 Birth Cohort, and 204 CT and 241 MR scans from participants of the Memory Clinic Cohort, Singapore. We tested associations between six CT-based volumetric measures (CTVMs) and existing clinical diagnoses, fluid and imaging biomarkers, and measures of cognition.RESULTSCTVMs differentiated cognitively healthy individuals from dementia and prodromal dementia patients with high accuracy levels comparable to MR-based measures. CTVMs were significantly associated with measures of cognition and biochemical markers of neurodegeneration.DISCUSSIONThese findings suggest the potential future use of CT-based volumetric measures as an informative first-line examination tool for neurodegenerative disease diagnostics after further validation.HIGHLIGHTSComputed tomography (CT)-based volumetric measures can distinguish between patients with neurodegenerative disease and healthy controls, as well as between patients with prodromal dementia and controls.CT-based volumetric measures associate well with relevant cognitive, biochemical, and neuroimaging markers of neurodegenerative diseases.Model performance, in terms of brain tissue classification, was consistent across two cohorts of diverse nature.Intermodality agreement between our automated CT-based and established magnetic resonance (MR)-based image segmentations was stronger than the agreement between visual CT and MR imaging assessment.
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| 8. |
- Tofiq, A., et al.
(författare)
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Effects of Peroral Omega-3 Fatty Acid Supplementation on Cerebrospinal Fluid Biomarkers in Patients with Alzheimer's Disease: A Randomized Controlled Trial-The OmegAD Study
- 2021
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Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 83:3, s. 1291-1301
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies have suggested a connection between a decrease in the levels of polyunsaturated fatty acids (PUFAs) and Alzheimer's disease (AD). We aimed to assess the effect of supplementation with omega-3 fatty acids (n-3 FAs) on biomarkers analyzed in the cerebrospinal fluid (CSF) of patients diagnosed with AD. Objective: To investigate the effects of daily supplementation with 2.3 g of PUFAs in AD patients on the biomarkers in CSF described below. We also explored the possible correlation between these biomarkers and the performance in the cognitive test Mini-Mental State Examination (MMSE). Methods: Thirty-three patients diagnosed with AD were randomized to either treatment with a daily intake of 2.3 g of n-3 FAs (n = 18) or placebo (n = 15). CSF samples were collected at baseline and after six months of treatment, and the following biomarkers were analyzed: A beta 38, A beta 40, A beta 42, t-tau, p-tau, neurofilament light (NfL), chitinase-3-like protein 1 (YKL-40), acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), soluble IL-1 receptor type II (sIL-1RII), and IL-6. Results: There were no significant differences between the groups concerning the level of the different biomarkers in the CSF at baseline. Within the treatment group, there was a small but significant increase in both YKL-40 (p = 0.04) and NfL (p = 0.03), while the other CSF biomarkers remained stable. Conclusion: Supplementation with n-3 FAs had a statistically significant effect on NfL and YKL-40, resulting in an increase of both biomarkers, indicating a possible increase of inflammatory response and axonal damage. This increase in biomarkers did not correlate with MMSE score.
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