Reduced cerebrospinal fluid dynorphin A1–8 in Alzheimer's disease

Sunderland, Trey; Berrettini, Wade H.; Molchan, Susan E.; Lawlor, Brian A.; Martínez, Rick A.; Vitiello, Benedetto; Tariot, Pierre N.; Cohen, Robert M.

doi:10.1016/0006-3223(91)90073-u

Cited by 16 publications

(4 citation statements)

References 32 publications

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“…The Alzheimer patients revealed a 40% decrease in the CSF Dyn A (1-8) compared to controls. This finding was further supported when an additional 20 SDAT patients with similar clinical backgrounds also showed reduced CSF level of the opioid octapeptide (95). The measured CSF level of Dyn A (1-8) did not correlate significantly with clinical variables or CSF measures of monoamine metabolites.…”

Section: Opioid Peptides In Neurodegenerative Disordersmentioning

confidence: 79%

“…The recorded activity significantly correlated with psychological functions when examined using a dementia rating scale and it was suggested that beta-End is associated with the pathophysiology of dementia. This original study was followed by several others indicating decreased CSF levels of beta-End in SDAT (89)(90)(91)(92)(93)(94)(95)(96). In studies of beta-End in CSF from both SDAT and patients with multi-infarct dementia it was found that the peptide level was decreased in both groups of patients suggesting that low CSF ß-End level may be generally related to dementia (89).…”

Section: Opioid Peptides In Neurodegenerative Disordersmentioning

confidence: 95%

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Opioid peptides in cerebrospinal fluid-methods for analysis and their significance in the clinical perspective

Nyberg

2004

Front Biosci

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The discovery of the endogenous opioid peptide systems and their subsequent identification in human cerebrospinal fluid near 30 years ago triggered an intensive research to evaluate the function of these compounds in the clinical perspective. However, for this purpose it was necessary to develop reliable techniques with high sensitivity and reproducibility. Furthermore, it was necessary to assess the chemical nature of the opioid activity present in CSF. Therefore, research on opioid peptides in CSF have to a considerable extent been directed to attempts to characterize the peptide activity present in this fluid in order to identify suitable markers of activity in any particular opioid peptide system. In the clinic these markers have been used in attempts to correlate alterations in peptide levels to various neurological diseases. This article reviews the past and ongoing research on opioid peptide systems in CSF from human with particular emphasis on their relevance in the clinical perspective.

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Section: Opioid Peptides In Neurodegenerative Disordersmentioning

confidence: 79%

Section: Opioid Peptides In Neurodegenerative Disordersmentioning

confidence: 95%

Opioid peptides in cerebrospinal fluid-methods for analysis and their significance in the clinical perspective

Nyberg

2004

Front Biosci

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“…Opioid receptor kappa 1 ( OPRK1 ) regulates cognitive and learning processes by inhibiting neurotransmitter release [ 24 ]. Moreover, there is a greater number of OPRK1 binding sites in the limbic system in AD brains than in healthy subjects [ 25 ]. There were no statistically significant differences in OPRK1 mRNA levels between non-NDD subjects and patients with AD, PD, or VaD/mixed dementia ( Figure 1 E).…”

Section: Resultsmentioning

confidence: 99%

Gene Expression Profiling as a Novel Diagnostic Tool for Neurodegenerative Disorders

Martínez-Iglesias

Naidoo

Carril

et al. 2023

IJMS

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There is a lack of effective diagnostic biomarkers for neurodegenerative disorders (NDDs). Here, we established gene expression profiles for diagnosing Alzheimer’s disease (AD), Parkinson’s disease (PD), and vascular (VaD)/mixed dementia. Patients with AD had decreased APOE, PSEN1, and ABCA7 mRNA expression. Subjects with VaD/mixed dementia had 98% higher PICALM mRNA levels, but 75% lower ABCA7 mRNA expression than healthy individuals. Patients with PD and PD-related disorders showed increased SNCA mRNA levels. There were no differences in mRNA expression for OPRK1, NTRK2, and LRRK2 between healthy subjects and NDD patients. APOE mRNA expression had high diagnostic accuracy for AD, and moderate accuracy for PD and VaD/mixed dementia. PSEN1 mRNA expression showed promising accuracy for AD. PICALM mRNA expression was less accurate as a biomarker for AD. ABCA7 and SNCA mRNA expression showed high-to-excellent diagnostic accuracy for AD and PD, and moderate-to-high accuracy for VaD/mixed dementia. The APOE E4 allele reduced APOE expression in patients with different APOE genotypes. There was no association between PSEN1, PICALM, ABCA7, and SNCA gene polymorphisms and expression. Our study suggests that gene expression analysis has diagnostic value for NDDs and provides a liquid biopsy alternative to current diagnostic methods.

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“…Given GAL’s role in inhibiting DA neuron activities, it is reasonable to expect downregulated GAL levels in affected neurons, potentially compensating for the degenerated dopaminergic function caused by GCase deficiency. It is worth noting that GAL levels in CSF of AD patients were not altered [ 75 , 76 ].…”

Section: Discussionmentioning

confidence: 99%

Secretome Analyses Identify FKBP4 as a GBA1-Associated Protein in CSF and iPS Cells from Parkinson’s Disease Patients with GBA1 Mutations

Kojima,

Paslawski,

Lyu

et al. 2024

IJMS

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Mutations in the GBA1 gene increase the risk of developing Parkinson’s disease (PD). However, most carriers of GBA1 mutations do not develop PD throughout their lives. The mechanisms of how GBA1 mutations contribute to PD pathogenesis remain unclear. Cerebrospinal fluid (CSF) is used for detecting pathological conditions of diseases, providing insights into the molecular mechanisms underlying neurodegenerative disorders. In this study, we utilized the proximity extension assay to examine the levels of metabolism-linked protein in the CSF from 17 PD patients carrying GBA1 mutations (GBA1-PD) and 17 idiopathic PD (iPD). The analysis of CSF secretome in GBA1-PD identified 11 significantly altered proteins, namely FKBP4, THOP1, GLRX, TXNDC5, GAL, SEMA3F, CRKL, APLP1, LRP11, CD164, and NPTXR. To investigate GBA1-associated CSF changes attributed to specific neuronal subtypes responsible for PD, we analyzed the cell culture supernatant from GBA1-PD-induced pluripotent stem cell (iPSC)-derived midbrain dopaminergic (mDA) neurons. The secretome analysis of GBA1-PD iPSC-derived mDA neurons revealed that five differently regulated proteins overlapped with those identified in the CSF analysis: FKBP4, THOP1, GLRX, GAL, and CRKL. Reduced intracellular level of the top hit, FKPB4, was confirmed via Western Blot. In conclusion, our findings identify significantly altered CSF GBA1-PD-associated proteins with FKPB4 being firmly attributed to mDA neurons.

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Reduced cerebrospinal fluid dynorphin A1–8 in Alzheimer's disease

Cited by 16 publications

References 32 publications

Opioid peptides in cerebrospinal fluid-methods for analysis and their significance in the clinical perspective

Opioid peptides in cerebrospinal fluid-methods for analysis and their significance in the clinical perspective

Gene Expression Profiling as a Novel Diagnostic Tool for Neurodegenerative Disorders

Secretome Analyses Identify FKBP4 as a GBA1-Associated Protein in CSF and iPS Cells from Parkinson’s Disease Patients with GBA1 Mutations

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