Telephone Assessment of Cognitive Function in the Late-Onset Alzheimer's Disease Family Study

Abstract The discovery of treatments to prevent or delay Alzheimer’s disease is a priority. The gene APOE is associated with cognitive change and late onset Alzheimer’s disease, and epidemiological studies have shown that the e_2 allele of APOE has a neuroprotective effect, and it is associated with increased longevity. We correlated APOE genotype data of 222 New England Centenarian Study participants, including 79 centenarians, 84 centenarian offspring and 55 carriers of APOE e_2, with aptamer-based serum proteomics (SomaLogic technology) of 4783 human proteins corresponding to 4137 genes. We discovered a signature of 16 proteins that associated with different APOE genotypes, and replicated the signature in 3 independent studies. We show that the protein signature tracks with gene expression profiles in brains of late onset Alzheimer’s disease vs. healthy controls. Finally, we show that seven of these proteins correlate with cognitive function changes. Therefore, targeting APOE e_2 molecularly may preserve cognitive function.

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A Chronological Review of Potential Disease-Modifying Therapeutic Strategies for Alzheimer's Disease

Current Pharmaceutical Design ◽

10.2174/1381612826666200211121416 ◽

2020 ◽

Vol 26 (12) ◽

pp. 1286-1299 ◽

Cited By ~ 3

Author(s):

Miren Ettcheto ◽

Oriol Busquets ◽

Triana Espinosa-Jiménez ◽

Ester Verdaguer ◽

Carme Auladell ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Function ◽

Neurodegenerative Disorder ◽

Late Onset ◽

Wide Spectrum ◽

Amyloid Β ◽

Amyloid Β Protein ◽

New Therapeutic Approaches ◽

Β Protein

: Late-onset Alzheimer’s disease (LOAD) is a neurodegenerative disorder that has become a worldwide health problem. This pathology has been classically characterized for its affectation on cognitive function and the presence of depositions of extracellular amyloid β-protein (Aβ) and intracellular neurofibrillary tangles (NFT) composed of hyperphosphorylated Tau protein. To this day, no effective treatment has been developed. : Multiple strategies have been proposed over the years with the aim of finding new therapeutic approaches, such as the sequestration of Aβ in plasma or the administration of anti-inflammatory drugs. Also, given the significant role of the insulin receptor in the brain in the proper maintenance of cognitive function, drugs focused on the amelioration of insulin resistance have been proposed as potentially useful and effective in the treatment of AD. In the present review, taking into account the molecular complexity of the disease, it has been proposed that the most appropriate therapeutic strategy is a combinatory treatment of several drugs that will regulate a wide spectrum of the described altered pathological pathways.

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Association between cognitive function, behavioral syndromes and two-year clinical outcome in Chinese subjects with late-onset Alzheimer's disease

International Psychogeriatrics ◽

10.1017/s1041610205002930 ◽

2006 ◽

Vol 18 (03) ◽

pp. 517 ◽

Cited By ~ 15

Author(s):

Linda C. W. Lam ◽

Tony Leung ◽

Victor W. C. Lui ◽

Vivian P. Y. Leung ◽

Helen F. K. Chiu

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Function ◽

Clinical Outcome ◽

Late Onset ◽

Behavioral Syndromes ◽

Chinese Subjects

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Engagement of TREM2 by a novel monoclonal antibody induces activation of microglia and improves cognitive function in Alzheimer’s disease models

Journal of Neuroinflammation ◽

10.1186/s12974-020-01980-5 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Michael Fassler ◽

Maya Saban Rappaport ◽

Clara Benaim Cuño ◽

Jacob George

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Monoclonal Antibody ◽

Cognitive Function ◽

Cellular Proliferation ◽

Late Onset ◽

Intracerebral Injection ◽

Dependent Manner ◽

Soluble Trem2 ◽

Membrane Bound

Abstract Background Genetic variants and mutations in triggering receptor expressed in myeloid cells (TREM2) are associated with premature and late onset Alzheimer’s disease (AD). Methods We developed a panel of monoclonal antibodies, the selected lead of which was avidly shown to bind the extracellular domain of human and murine TREM2. Results By engaging membrane-bound TREM2, the selected antibody was shown to promote their cellular proliferation, uptake of oligomeric beta amyloid/apoptotic neurons, and activation in a Syk and Akt dependent manner. The antibody was shown to avidly bind soluble TREM2 in the CSF from AD patients and blunted the proinflammatory program driven by its intracerebral injection. Upon in vivo treatment, the antibody was shown to improve cognitive function in experimental amyloidopathy models and to facilitate plaque-associated microglial coverage and activation. Conclusion Thus, we describe a novel monoclonal antibody targeting membrane bound and soluble TREM2, that improves cognitive function by inducing microglial activation and attenuating chronic neuroinflammation.

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