scholarly journals Lipid Metabolism and Alzheimer's Disease: Clinical Evidence, Mechanistic Link and Therapeutic Promise

FEBS Journal ◽  
2022 ◽  
Author(s):  
Fei Yin
Author(s):  
N. J. Hutchinson

In recent years, advances in medical, surgical and nursing care have resulted in a dramatic increase in the life expectancy of children born with Down's syndrome (DS), giving rise to an older population of people with DS not previously seen. It has become clear from the study of the ageing DS population that an association exists between DS and Alzheimer's disease (AD). This paper reviews neuropathological and clinical evidence of an association between DS and AD. The clinical features of AD in people with DS and apparent differences between the signs and symptoms of AD seen in individuals with DS and older people with AD in the general population are discussed. Issues pertaining to the diagnosis of AD in people with DS, such as diagnostic criteria, the process of diagnosis, and specific problems of diagnosing AD in people with DS are also discussed. The therapeutic needs of individuals with DS who are diagnosed as having AD are considered and the necessity to strive to make the diagnostic procedure as valid as possible is expressed. The paper concludes that neuropsychological testing has an important role to play in the diagnostic process.


2013 ◽  
Vol 536 ◽  
pp. 90-95 ◽  
Author(s):  
James D. Mills ◽  
Thomas Nalpathamkalam ◽  
Heidi I.L. Jacobs ◽  
Caroline Janitz ◽  
Daniele Merico ◽  
...  

Author(s):  
Clyde F. Phelix ◽  
Richard G. LeBaron ◽  
Dawnlee J. Roberson ◽  
Rosa E. Villanueva ◽  
Greg Villareal ◽  
...  

The authors had validated a proprietary method, Transcriptome-To-Metabolome™ (TTM™) Biosimulation, for using the transcriptome to determine parameters for kinetic biosimulation of 16 core metabolic pathways. In vivo and in silico evidence confirmed that hippocampal cholesterol metabolism decreases with aging and increases with Alzheimer’s disease (AD). The molecular studies on aging primate and human hippocampus, including AD samples, provided internal validations on the biosimulations, while evidence from the literature, bibliome, provided external validations. This study extends the investigations with the TTM™ Biosimulations into the changes in these 16 metabolic pathways in aging male human hippocampus and for stages of AD. The authors report robust hippocampal hypometabolism in the fifth to tenth decade of life involving glucose and lipid metabolism in male humans. These findings are validated externally from the bibliome. Several changes in AD are demonstrated to be exaggerations or deviations of very late stage changes of normal aging among these pathways.


2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Jin Xu ◽  
◽  
Giulia Bankov ◽  
Min Kim ◽  
Asger Wretlind ◽  
...  

Abstract Background There is an urgent need to understand the pathways and processes underlying Alzheimer’s disease (AD) for early diagnosis and development of effective treatments. This study was aimed to investigate Alzheimer’s dementia using an unsupervised lipid, protein and gene multi-omics integrative approach. Methods A lipidomics dataset comprising 185 AD patients, 40 mild cognitive impairment (MCI) individuals and 185 controls, and two proteomics datasets (295 AD, 159 MCI and 197 controls) were used for weighted gene co-expression network analyses (WGCNA). Correlations of modules created within each modality with clinical AD diagnosis, brain atrophy measures and disease progression, as well as their correlations with each other, were analyzed. Gene ontology enrichment analysis was employed to examine the biological processes and molecular and cellular functions of protein modules associated with AD phenotypes. Lipid species were annotated in the lipid modules associated with AD phenotypes. The associations between established AD risk loci and the lipid/protein modules that showed high correlation with AD phenotypes were also explored. Results Five of the 20 identified lipid modules and five of the 17 identified protein modules were correlated with clinical AD diagnosis, brain atrophy measures and disease progression. The lipid modules comprising phospholipids, triglycerides, sphingolipids and cholesterol esters were correlated with AD risk loci involved in immune response and lipid metabolism. The five protein modules involved in positive regulation of cytokine production, neutrophil-mediated immunity, and humoral immune responses were correlated with AD risk loci involved in immune and complement systems and in lipid metabolism (the APOE ε4 genotype). Conclusions Modules of tightly regulated lipids and proteins, drivers in lipid homeostasis and innate immunity, are strongly associated with AD phenotypes.


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