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- Rosén, Christoffer, 1986, et al.
(författare)
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Cerebrospinal fluid biomarkers for pathological processes in Alzheimer's disease
- 2013
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Ingår i: Current Opinion in Psychiatry. - 0951-7367. ; 26:3, s. 276-282
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Tidskriftsartikel (refereegranskat)abstract
- Purpose of review: To review the rationale behind and the use of cerebrospinal fluid (CSF) biomarkers in Alzheimer's disease (AD). Established as well as new candidate biomarkers will be covered. Recent findings: AD is a complex disorder and the AD brain is characterized by multiple pathological processes, in addition to well-described plaque and tangle diseases. Recent studies have tried to address this by evaluating biomarkers related to features such as neuroinflammation, oxidative stress, microglial activation and synaptic degeneration, with some positive results. Summary: The CSF biomarkers total tau, phosphorylated-tau and the 42 amino acid isoform of amyloid beta reflect core elements of AD, that is, axonal degeneration, tangle disease and senile plaques, have been thoroughly tested and provide high diagnostic accuracy in the discrimination of patients with AD as compared with cognitively normal controls. They are also highly predictive of AD with dementia in patients with mild cognitive impairment, and have been included in new diagnostic criteria. New biomarkers may add to their diagnostic performance. Other potential fields of use include the monitoring of disease progression or pharmacodynamic drug effects. A common denominator for the candidate biomarkers is the need for validation in further studies to clarify their potential.
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| 2. |
- Rosén, Christoffer, 1986, et al.
(författare)
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Fluid biomarkers in Alzheimer's disease - current concepts
- 2013
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Ingår i: Molecular Neurodegeneration. - : Springer Science and Business Media LLC. - 1750-1326. ; 8:20
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Tidskriftsartikel (refereegranskat)abstract
- The diagnostic guidelines of Alzheimer's disease (AD) have recently been updated to include brain imaging and cerebrospinal fluid (CSF) biomarkers, with the aim of increasing the certainty of whether a patient has an ongoing AD neuropathologic process or not. The CSF biomarkers total tau (T-tau), hyperphosphorylated tau (P-tau) and the 42 amino acid isoform of amyloid beta (A beta 42) reflect the core pathologic features of AD, which are neuronal loss, intracellular neurofibrillary tangles and extracellular senile plaques. Since the pathologic processes of AD start decades before the first symptoms, these biomarkers may provide means of early disease detection. The updated guidelines identify three different stages of AD: preclinical AD, mild cognitive impairment (MCI) due to AD and AD with dementia. In this review, we aim to summarize the CSF biomarker data available for each of these stages. We also review results from blood biomarker studies. In summary, the core AD CSF biomarkers have high diagnostic accuracy both for AD with dementia and to predict incipient AD (MCI due to AD). Longitudinal studies on healthy elderly and recent cross-sectional studies on patients with dominantly inherited AD mutations have also found biomarker changes in cognitively normal at-risk individuals. This will be important if disease-modifying treatment becomes available, given that treatment will probably be most effective early in the disease. An important prerequisite for this is trustworthy analyses. Since measurements vary between studies and laboratories, standardization of analytical as well as pre-analytical procedures will be essential. This process is already initiated. Apart from filling diagnostic roles, biomarkers may also be utilized for prognosis, disease progression, development of new treatments, monitoring treatment effects and for increasing the knowledge about pathologic processes coupled to the disease. Hence, the search for new biomarkers continues. Several candidate biomarkers have been found in CSF, and although biomarkers in blood have been harder to find, some recent studies have presented encouraging results. But before drawing any major conclusions, these results need to be verified in independent studies.
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