| 1. |
- Portelius, Erik, 1977, et al.
(författare)
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Characterization of tau in cerebrospinal fluid using mass spectrometry.
- 2008
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Ingår i: Journal of proteome research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 7:5, s. 2114-20
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Tidskriftsartikel (refereegranskat)abstract
- The neurodegenerative disorder Alzheimer's disease (AD) is the most common cause of dementia in the elderly. The presence of neurofibrillary tangles, consisting of hyperphosphorylated tau protein, is one of the major neuropathologic characteristics of the disease, making this protein an attractive biomarker for AD and a possible target for therapy. Here, we describe an optimized immunoprecipitation mass spectrometry method that enables, for the first time, detailed characterization of tau in human cerebrospinal fluid. The identities of putative tau fragments were confirmed using nanoflow liquid chromatography and tandem mass spectrometry. Nineteen tryptic fragments of tau were detected, of which 16 are found in all tau isoforms while 3 represented unique tau isoforms. These results pave the way for clinical CSF studies on the tauopathies.
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| 2. |
- Öhrfelt Olsson, Annika, 1973, et al.
(författare)
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Cerebrospinal fluid alpha-synuclein in neurodegenerative disorders-a marker of synapse loss?
- 2009
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Ingår i: Neuroscience letters. - : Elsevier BV. - 0304-3940. ; 450:3, s. 332-5
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Tidskriftsartikel (refereegranskat)abstract
- The association of alpha-synuclein (alpha-syn) neuropathology with Parkinson's disease (PD) and several related disorders has led to an intense research effort to develop cerebrospinal fluid (CSF)- or blood-based alpha-syn biomarkers for these types of diseases. Recent studies show that alpha-syn is present in CSF and possible to measure using enzyme-linked immunosorbent assay (ELISA). Here, we describe a novel ELISA that allows for quantification of alpha-syn in CSF down to 50pg/mL. The diagnostic value of the test was assessed using CSF samples from 66 Alzheimer's disease (AD) patients, 15PD patients, 15 patients with dementia with Lewy bodies (DLB) and 55 cognitively normal controls. PD and DLB patients and controls displayed similar CSF alpha-syn levels. AD patients had significantly lower alpha-syn levels than controls (median [inter-quartile range] 296 [234-372] and 395 [298-452], respectively, p<0.001). Moreover, AD patients with mini-mental state examination (MMSE) scores below 20 had significantly lower alpha-syn than AD patients with MMSE scores of 20 or higher (p=0.02). There was also a tendency towards a negative correlation between alpha-syn levels and disease duration in the AD group (r=-0.247, p=0.06). Altogether, our results speak against CSF alpha-syn as a reliable biomarker for PD and DLB. The lower alpha-syn levels in AD, as well as the association of alpha-syn reduction with AD severity, approximated by MMSE, suggests that it may be a general marker of synapse loss, a hypothesis that warrants further investigation.
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