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| 2. |
- Lautner, Ronald, et al.
(författare)
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Apolipoprotein e genotype and the diagnostic accuracy of cerebrospinal fluid biomarkers for Alzheimer disease.
- 2014
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 71:10, s. 1183-91
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Tidskriftsartikel (refereegranskat)abstract
- Several studies suggest that the apolipoprotein E (APOE) ε4 allele modulates cerebrospinal fluid (CSF) levels of β-amyloid 42 (Aβ42). Whether this effect is secondary to the association of the APOE ε4 allele with cortical Aβ deposition or whether APOE ε4 directly influences CSF levels of Aβ42 independently of Aβ pathology remains unknown.
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| 3. |
- Lautner, Ronald, et al.
(författare)
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Biomarkers for microglial activation in Alzheimer's disease.
- 2011
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Ingår i: International journal of Alzheimer's disease. - : Hindawi Limited. - 2090-0252. ; 2011
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Tidskriftsartikel (refereegranskat)abstract
- Intensive research over the last decades has provided increasing evidence for neuroinflammation as an integral part in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD). Inflammatory responses in the central nervous system (CNS) are initiated by activated microglia, representing the first line of the innate immune defence of the brain. Therefore, biochemical markers of microglial activation may help us understand the underlying mechanisms of neuroinflammation in AD as well as the double-sided qualities of microglia, namely, neuroprotection and neurotoxicity. In this paper we summarize candidate biomarkers of microglial activation in AD along with a survey of recent neuroimaging techniques.
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| 4. |
- Lautner, Ronald, et al.
(författare)
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Preclinical effects of APOE ϵ4 on cerebrospinal fluid Aβ42 concentrations
- 2017
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Ingår i: Alzheimer's Research and Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: From earlier studies it is known that the APOE ϵ2/ϵ3/ϵ4 polymorphism modulates the concentrations of cerebrospinal fluid (CSF) beta-amyloid1-42 (Aβ42) in patients with cognitive decline due to Alzheimer's disease (AD), as well as in cognitively healthy controls. Here, in a large cohort consisting solely of cognitively healthy individuals, we aimed to evaluate how the effect of APOE on CSF Aβ42 varies by age, to understand the association between APOE and the onset of preclinical AD. Methods: APOE genotype and CSF Aβ42 concentration were determined in a cohort comprising 716 cognitively healthy individuals aged 17-99 from nine different clinical research centers. Results: CSF concentrations of Aβ42 were lower in APOE ϵ4 carriers than in noncarriers in a gene dose-dependent manner. The effect of APOE ϵ4 on CSF Aβ42 was age dependent. The age at which CSF Aβ42 concentrations started to decrease was estimated at 50 years in APOE ϵ4-negative individuals and 43 years in heterozygous APOE ϵ4 carriers. Homozygous APOE ϵ4 carriers showed a steady decline in CSF Aβ42 concentrations with increasing age throughout the examined age span. Conclusions: People possessing the APOE ϵ4 allele start to show a decrease in CSF Aβ42 concentration almost a decade before APOE ϵ4 noncarriers already in early middle age. Homozygous APOE ϵ4 carriers might deposit Aβ42 throughout the examined age span. These results suggest that there is an APOE ϵ4-dependent period of early alterations in amyloid homeostasis, when amyloid slowly accumulates, that several years later, together with other downstream pathological events such as tau pathology, translates into cognitive decline.
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| 5. |
- Mattsson, Niklas, et al.
(författare)
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Effects of APOE ε4 on neuroimaging, cerebrospinal fluid biomarkers, and cognition in prodromal Alzheimer's disease
- 2018
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 71, s. 81-90
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein (APOE) ε4 is a major genetic risk factor for Alzheimer's disease (AD), but its importance for the clinical and biological heterogeneity in AD is unclear, particularly at the prodromal stage. We analyzed 151 prodromal AD patients (44 APOE ε4-negative and 107 APOE ε4-positive) from the BioFINDER study. We tested cognition, 18F-flutemetamol β-amyloid (Aβ) positron emission tomography, cerebrospinal fluid biomarkers of Aβ tau and neurodegeneration, and magnetic resonance imaging of white matter pathology and brain structure. Despite having similar cortical Aβ-load and baseline global cognition (mini mental state examination), APOE ε4-negative prodromal AD had more nonamnestic cognitive impairment, higher cerebrospinal fluid levels of Aβ-peptides and neuronal injury biomarkers, more white matter pathology, more cortical atrophy, and faster decline of mini mental state examination, compared to APOE ε4-positive prodromal AD. The absence of APOE ε4 is associated with an atypical phenotype of prodromal AD. This suggests that APOE ε4 may impact both the diagnostics of AD in early stages and potentially also effects of disease-modifying treatments.
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| 6. |
- Nagy, Karin, et al.
(författare)
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Cerebrospinal fluid analyses for the diagnosis of subarachnoid haemorrhage and experience from a Swedish study. What method is preferable when diagnosing a subarachnoid haemorrhage?
- 2013
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Ingår i: Clinical chemistry and laboratory medicine : CCLM / FESCC. - : Walter de Gruyter GmbH. - 1434-6621 .- 1437-4331. ; 51:11, s. 2073-2086
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Subarachnoid haemorrhage (SAH) has a high mortality and morbidity rate. Early SAH diagnosis allows the early treatment of a ruptured cerebral aneurysm, which improves the prognosis. Diagnostic cerebrospinal fluid (CSF) analyses may be performed after a negative computed tomography scan, but the precise analytical methods to be used have been debated. Here, we summarize the scientific evidence for different CSF methods for SAH diagnosis and describe their implementation in different countries. The principle literature search was conducted using PubMed and Scopus with the search items "cerebrospinal fluid", "subarachnoid haemorrhage", and "diagnosis". CSF analyses for SAH include visual examination, red blood cell counts, spectrophotometry for oxyhaemoglobin or bilirubin determination, CSF cytology, and ferritin measurement. The methods vary in availability and performance. There is a consensus that spectrophotometry has the highest diagnostic performance, but both oxyhaemoglobin and bilirubin determinations are susceptible to important confounding factors. Visual inspection of CSF for xanthochromia is still frequently used for diagnosis of SAH, but it is advised against because spectrophotometry has a superior diagnostic accuracy. A positive finding of CSF bilirubin is a strong indicator of an intracranial bleeding, whereas a positive finding of CSF oxyhaemoglobin may indicate an intracranial bleeding or a traumatic tap. Where spectrophotometry is not available, the combination of CSF cytology for erythrophages or siderophages and ferritin is a promising alternative.
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| 7. |
- Skillbäck, Tobias, et al.
(författare)
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Apolipoprotein E genotypes and longevity across dementia disorders
- 2018
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Ingår i: Alzheimer's & Dementia. - : Elsevier. - 1552-5260 .- 1552-5279. ; 14:7, s. 895-901
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The ε4 allele of the apolipoprotein E (APOE) gene is a prominent risk factor for Alzheimer's disease (AD), but its implication in other dementias is less well studied.METHODS: We used a data set on 2858 subjects (1098 AD, 260 vascular dementia [VaD], 145 mixed AD and VaD, 90 other dementia diagnoses, and 1265 controls) to examine the association of APOE polymorphisms with clinical dementia diagnoses, biomarker profiles, and longevity.RESULTS: The ε4 allele was associated with reduced longevity as ε4 versus ε3 homozygotes lived on average 2.6 years shorter (P = .006). In AD, ε4 carriers lived 1.0 years shorter than noncarriers (P = .028). The ε4 allele was more prevalent in AD, mixed AD and VaD, and VaD patients compared to controls, but not in other dementia disorders.DISCUSSION: The APOE ε4 allele is influential in AD but might also be of importance in VaD and in mixed AD and VaD, diseases in which concomitant AD pathology is common.
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| 8. |
- Zetterberg, Henrik, 1973, et al.
(författare)
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CSF in Alzheimer's Disease
- 2014
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Ingår i: Advances in Clinical Chemistry. - San Diego : Elsevier Academic Press Inc. - 0065-2423. ; 65, s. 143-172
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Forskningsöversikt (refereegranskat)abstract
- Alzheimer's disease (AD) is a progressive brain amyloidosis that injures brain regions involved in memory consolidation and other cognitive functions. Neuropathologically, the disease is characterized by accumulation of a 42-amino acid protein called amyloid beta, and N-terminally truncated fragments thereof, in extracellular senile plaques together with intraneuronal inclusions of hyperphosphorylated tau protein in neurofibrillary tangles, and neuronal and axonal degeneration and loss. Clinical chemistry tests for these pathologies have been developed for use on cerebrospinal fluid samples. Here, we review what these markers have taught us on the disease process in AD and how they can be implemented in routine clinical chemistry. We also provide an update on new marker development and ongoing analytical standardization effort.
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| 9. |
- Zetterberg, Henrik, 1973, et al.
(författare)
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CSF in Alzheimer's Disease
- 2014
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Ingår i: Advances in Clinical Chemistry. Volume 65. Gregory S. Makowski (Ed.). - : Academic Press Inc.. - 9780128022665 ; , s. 143-172
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Alzheimer's disease (AD) is a progressive brain amyloidosis that injures brain regions involved in memory consolidation and other cognitive functions. Neuropathologically, the disease is characterized by accumulation of a 42-amino acid protein called amyloid β, and N-terminally truncated fragments thereof, in extracellular senile plaques together with intraneuronal inclusions of hyperphosphorylated tau protein in neurofibrillary tangles, and neuronal and axonal degeneration and loss. Clinical chemistry tests for these pathologies have been developed for use on cerebrospinal fluid samples. Here, we review what these markers have taught us on the disease process in AD and how they can be implemented in routine clinical chemistry. We also provide an update on new marker development and ongoing analytical standardization effort. © 2014 Elsevier Inc.
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