Dissecting Complex and Multifactorial Nature of Alzheimer’s Disease Pathogenesis: a Clinical, Genomic, and Systems Biology Perspective

Alzheimer's disease (AD) is the most common form of dementia. Even with its well-known symptoms of memory loss and well-characterized pathology of beta amyloid (Aβ) plaques and neurofibrillary tangles, the disease pathogenesis and initiating factors are still not well understood. To tackle this problem, a systems biology model has been developed and used to study the varying effects of variations in the ApoE allele present, as well as the effects of short term and periodic inflammation at low to moderate levels. Simulations showed a late onset peak of Aβ in the ApoE4 case that lead to localized neuron loss which could be ameliorated in part by application of short-term pro-inflammatory mediators. The model that has been developed herein represents one of the first attempts to model AD from a systems approach to study physiologically relevant parameters that may prove useful to physicians in the future.

Download Full-text

Endosomal‐lysosomal dysfunctions in Alzheimer’s disease: Pathogenesis and therapeutic interventions

Metabolic Brain Disease ◽

10.1007/s11011-021-00737-0 ◽

2021 ◽

Author(s):

Shereen Shi Min Lai ◽

Khuen Yen Ng ◽

Rhun Yian Koh ◽

Kian Chung Chok ◽

Soi Moi Chye

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Therapeutic Interventions ◽

Disease Pathogenesis

Download Full-text

Alzheimer’s Disease Pathogenesis: Role of Autophagy and Mitophagy Focusing in Microglia

International Journal of Molecular Sciences ◽

10.3390/ijms22073330 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3330

Author(s):

Mehdi Eshraghi ◽

Aida Adlimoghaddam ◽

Amir Mahmoodzadeh ◽

Farzaneh Sharifzad ◽

Hamed Yasavoli-Sharahi ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Therapeutic Target ◽

Neurological Disorder ◽

Inflammatory Cells ◽

Disease Pathogenesis ◽

Current Review ◽

The Brain ◽

Comprehensive Discussion

Alzheimer’s disease (AD) is a debilitating neurological disorder, and currently, there is no cure for it. Several pathologic alterations have been described in the brain of AD patients, but the ultimate causative mechanisms of AD are still elusive. The classic hallmarks of AD, including am-yloid plaques (Aβ) and tau tangles (tau), are the most studied features of AD. Unfortunately, all the efforts targeting these pathologies have failed to show the desired efficacy in AD patients so far. Neuroinflammation and impaired autophagy are two other main known pathologies in AD. It has been reported that these pathologies exist in AD brain long before the emergence of any clinical manifestation of AD. Microglia are the main inflammatory cells in the brain and are considered by many researchers as the next hope for finding a viable therapeutic target in AD. Interestingly, it appears that the autophagy and mitophagy are also changed in these cells in AD. Inside the cells, autophagy and inflammation interact in a bidirectional manner. In the current review, we briefly discussed an overview on autophagy and mitophagy in AD and then provided a comprehensive discussion on the role of these pathways in microglia and their involvement in AD pathogenesis.

Download Full-text