Acute response to cholinergic challenge predicts long‐term response to galantamine treatment in patients with Alzheimer’s Disease

Depression is a common neuropsychiatric manifestation among Alzheimer’s disease (AD) patients. It may compromise everyday activities and lead to a faster cognitive decline as well as worse quality of life. The identification of promising biomarkers may therefore help to timely initiate and improve the treatment of preclinical and clinical states of AD, and to improve the long-term functional outcome. In this narrative review, we report studies that investigated biomarkers for AD-related depression. Genetic findings state AD-related depression as a rather complex, multifactorial trait with relevant environmental and inherited contributors. However, one specific set of genes, the brain derived neurotrophic factor (BDNF), specifically the Val66Met polymorphism, may play a crucial role in AD-related depression. Regarding neuroimaging markers, the most promising findings reveal structural impairments in the cortico-subcortical networks that are related to affect regulation and reward / aversion control. Functional imaging studies reveal abnormalities in predominantly frontal and temporal regions. Furthermore, CSF based biomarkers are seen as potentially promising for the diagnostic process showing abnormalities in metabolic pathways that contribute to AD-related depression. However, there is a need for standardization of methodological issues and for replication of current evidence with larger cohorts and prospective studies.

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NF-κB as a Key Mediator of Brain Inflammation in Alzheimer’s Disease

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527316666170807130011 ◽

2019 ◽

Vol 18 (1) ◽

pp. 3-10 ◽

Cited By ~ 18

Author(s):

Chul Ju Hwang ◽

Dong-Young Choi ◽

Mi Hee Park ◽

Jin Tae Hong

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Treatment Strategies ◽

Close Correlation ◽

Specific Protein ◽

Brain Inflammation ◽

Cytokines And Chemokines ◽

Inflammatory Drugs ◽

Peptide Fibrils

Alzheimer’s disease is the most common form of dementia. It is characterized by betaamyloid peptide fibrils which are extracellular deposition of a specific protein, accompanied by extensive neuroinflammation. Various studies show the presence of a number of inflammation markers in the AD brain: elevated inflammatory cytokines and chemokines, and an accumulation of activated microglia in the damaged regions. NF-κB is a family of redox sensitive transcriptional factors, and it is known that NF-κB has binding sites in the promoter region of the genes involved in amyloidogenesis and inflammation. Long-term use of non-steroidal anti-inflammatory drugs prevents progression of AD and delays its onset, suggesting that there is a close correlation between NF-κB and AD pathogenesis. This study aims to (1) assess the association between NF-κB activity and AD through discussion of a variety of experimental and clinical studies on AD and (2) review treatment strategies designed to treat or prevent AD with NF-κB inhibitors.

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Neurobehavioral Consequences Associated with Long Term Tramadol Utilization and Pathological Mechanisms

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527318666191112124435 ◽

2020 ◽

Vol 18 (10) ◽

pp. 758-768 ◽

Cited By ~ 2

Author(s):

Khadga Raj ◽

Pooja Chawla ◽

Shamsher Singh

Keyword(s):

Alzheimer’S Disease ◽

Parkinson’S Disease ◽

Alzheimer's Disease ◽

Parkinson's Disease ◽

Serotonin Reuptake ◽

Selective Serotonin Reuptake Inhibitors ◽

Serotonin Syndrome ◽

Dopamine Synthesis ◽

Synthetic Analog

: Tramadol is a synthetic analog of codeine used to treat pain of moderate to severe intensity and is reported to have neurotoxic potential. At therapeutic dose, tramadol does not cause major side effects in comparison to other opioid analgesics, and is useful for the management of neurological problems like anxiety and depression. Long term utilization of tramadol is associated with various neurological disorders like seizures, serotonin syndrome, Alzheimer’s disease and Parkinson’s disease. Tramadol produces seizures through inhibition of nitric oxide, serotonin reuptake and inhibitory effects on GABA receptors. Extensive tramadol intake alters redox balance through elevating lipid peroxidation and free radical leading to neurotoxicity and produces neurobehavioral deficits. During Alzheimer’s disease progression, low level of intracellular signalling molecules like cGMP, cAMP, PKC and PKA affect both learning and memory. Pharmacologically tramadol produces actions similar to Selective Serotonin Reuptake Inhibitors (SSRIs), increasing the concentration of serotonin, which causes serotonin syndrome. In addition, tramadol also inhibits GABAA receptors in the CNS has been evidenced to interfere with dopamine synthesis and release, responsible for motor symptoms. The reduced level of dopamine may produce bradykinesia and tremors which are chief motor abnormalities in Parkinson’s Disease (PD).

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Learning Deficits Accompanied by Microglial Proliferation After the Long-Term Post-Injection of Alzheimer’s Disease Brain Extract in Mouse Brains

Journal of Alzheimer s Disease ◽

10.3233/jad-201002 ◽

2021 ◽

Vol 79 (4) ◽

pp. 1701-1711

Author(s):

Tetsuo Hayashi ◽

Shotaro Shimonaka ◽

Montasir Elahi ◽

Shin-Ei Matsumoto ◽

Koichi Ishiguro ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Brain ◽

Functional Decline ◽

Brain Regions ◽

Insoluble Fraction ◽

Brain Extract ◽

Post Injection ◽

Learning Deficits

Background: Human tauopathy brain injections into the mouse brain induce the development of tau aggregates, which spread to functionally connected brain regions; however, the features of this neurotoxicity remain unclear. One reason may be short observational periods because previous studies mostly used mutated-tau transgenic mice and needed to complete the study before these mice developed neurofibrillary tangles. Objective: To examine whether long-term incubation of Alzheimer’s disease (AD) brain in the mouse brain cause functional decline. Methods: We herein used Tg601 mice, which overexpress wild-type human tau, and non-transgenic littermates (NTg) and injected an insoluble fraction of the AD brain into the unilateral hippocampus. Results: After a long-term (17–19 months) post-injection, mice exhibited learning deficits detected by the Barnes maze test. Aggregated tau pathology in the bilateral hippocampus was more prominent in Tg601 mice than in NTg mice. No significant changes were observed in the number of Neu-N positive cells or astrocytes in the hippocampus, whereas that of Iba-I-positive microglia increased after the AD brain injection. Conclusion: These results potentially implicate tau propagation in functional decline and indicate that long-term changes in non-mutated tau mice may reflect human pathological conditions.

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