High Expression of Nicotinamide N-Methyltransferase in Patients with Sporadic Alzheimer’s Disease

AbstractWe have previously shown that the expression of nicotinamide N-methyltransferase (NNMT) is significantly increased in the brains of patients who have died of Parkinson’s disease (PD). In this study, we have compared the expression of NNMT in post-mortem medial temporal lobe, hippocampus and cerebellum of 10 Alzheimer’s disease (AD) and 9 non-disease control subjects using a combination of quantitative Western blotting, immunohistochemistry and dual-label confocal microscopy coupled with quantitative analysis of colocalisation. NNMT was detected as a single protein of 29 kDa in both AD and non-disease control brains, which was significantly increased in AD medial temporal lobe compared to non-disease controls (7.5-fold, P < 0.026). There was no significant difference in expression in the cerebellum (P = 0.91). NNMT expression in AD medial temporal lobe and hippocampus was present in cholinergic neurones with no glial localisation. Cell-type expression was identical in both non-disease control and AD tissues. These results are the first to show, in a proof-of-concept study using a small patient cohort, that NNMT protein expression is increased in the AD brain and is present in neurones which degenerate in AD. These results suggest that the elevation of NNMT may be a common feature of many neurodegenerative diseases. Confirmation of this overexpression using a larger AD patient cohort will drive the future development of NNMT-targetting therapeutics which may slow or stop the disease pathogenesis, in contrast to current therapies which solely address AD symptoms.

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Title Plasma Repressor Element 1-Silencing Transcription Factor Levels Decrease in Patients With Alzheimer's Disease

10.21203/rs.3.rs-215327/v1 ◽

2021 ◽

Author(s):

Mingqing Wei ◽

Jingnian Ni ◽

Jing Shi ◽

Ting Li ◽

Xiaoqing Xu ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Temporal Lobe ◽

Medial Temporal Lobe ◽

Medial Temporal Lobe Atrophy ◽

Protein Levels ◽

Significant Difference ◽

Amci Group ◽

Lobe Atrophy ◽

Repressor Element

Abstract Background: Repressor element 1-silencing transcription/neuron-restrictive silencer factor (REST) was considered as a new therapeutic target for neurodegenerative disorders like Alzheimer’s disease (AD). However, the relationships between AD and REST remain unclear. This study aimed to 1) examine plasma REST levels and REST gene AD patients, and 2) further explore the pathological relationships between REST protein levels and cognition decline in clinic, including medial temporal-lobe atrophy. Methods: Subjects (n=252, mean age 68.95±8.78 years old) were recruited in Beijing, China, and then divided into normal cognition (NC) group (n=89), amnestic mild cognitive impairment (aMCI) group (n=79) and AD group (n=84) according to diagnostic criteria. All subjects received neuropsychological assessments, laboratory tests and neuroimaging scans (MRI) at baseline. Plasma REST protein levels and distribution of the single-nucleotide polymorphisms (SNPs) of REST were compared across the three groups. Correlation between cognitive function, neuro-image and REST level was calculated using multi-linear-regression analysis. medial temporal-lobe atrophy (need to add this method). Results: The plasma REST levels in both NC group (430.30±303.43) and aMCI group (414.27±263.39) were significantly higher than AD group ( NC vs AD, p=0.034; aMCI vs AD, p=0.033). There was no significant difference between NC and aMCI group (p=0.948). There was no significant difference among three groups on the distribution of the genotype distribution of Rs2227902 and Rs3976529 of REST gene. The REST level was correlated to left medial temporal-lobe atrophy index (r=0.306, p=0.023). After 6-month follow up, the REST level in NC group was positively related to the change scores of mini-mental state examination scale (MMSE) (r=0.289, p=0.02). Conclusion: Plasma REST protein declines in AD patients, which also associated with memory impairment and left temporal-lobe atrophy, which may have potential value for clinical diagnosis of AD.

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Serum BDNF as a Potential Biomarker of Alzheimer's Disease: Verification Through Assessment of Serum, Cerebrospinal Fluid, and Medial Temporal Lobe Atrophy

Frontiers in Neurology ◽

10.3389/fneur.2021.653267 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yukiko Mori ◽

Mayumi Tsuji ◽

Tatsunori Oguchi ◽

Kensaku Kasuga ◽

Atsushi Kimura ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Temporal Lobe ◽

Medial Temporal Lobe ◽

Medial Temporal Lobe Atrophy ◽

Significant Difference ◽

Lobe Atrophy ◽

Serum Bdnf ◽

Mci Due To Ad

There is an urgent need to establish blood biomarkers for Alzheimer's disease (AD). Although it has been speculated that brain-derived neurotrophic factor (BDNF) is associated with AD, whether it can be used as a blood biomarker has yet to be determined. We used serum, cerebrospinal fluid (CSF), and medial temporal lobe atrophy from patients with AD to evaluate the association of BDNF with AD and assess its severity. For the blood analysis, 66 participants [21 normal controls (NCs) with normal cognitive function, 22 patients with mild cognitive impairment (MCI) due to AD, and 23 patients with AD] were included. For the CSF analysis, 30 participants were included. Magnetic resonance imaging, including a voxel-based specific regional analysis system for AD, and a Mini Mental State Examination were performed. Serum levels of BDNF and CSF levels of amyloid-β42, total tau, and phosphorylated tau were measured using ELISA. Serum BDNF levels were significantly lower in the MCI due to AD group than in the NC group (p = 0.037). Although there was no significant difference in the AD group, there was a downward trend compared to the NC group. Serum BDNF levels were positively correlated with CSF Aβ42 levels (r = 0.49, p = 0.005). There was a significant correlation between serum BDNF levels and medial temporal lobe atrophy. Decreased serum BDNF can potentially be used as a biomarker for early AD detection. Early detection of AD with a less invasive blood test is very beneficial, as it allows for intervention before dementia progresses.

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