Polyunsaturated Fatty Acids Mend Macrophage Transcriptome, Glycome, and Phenotype in the Patients with Neurodegenerative Diseases, Including Alzheimer’s Disease

Journal Article · Tue Nov 08 00:00:00 EST 2022 · Journal of Alzheimer's Disease

DOI:https://doi.org/10.3233/jad-220764· OSTI ID:2424564

Dover, Mary ^[1]; Moseley, Taylor ^[1]; Biskaduros, Adrienne ^[1]; Paulchakrabarti, Mousumi ^[2]; Hwang, Sung Hee ^[3]; Hammock, Bruce ^[3]; Choudhury, Biswa ^[2]; Kaczor-Urbanowicz, Karolina Elżbieta ^[4]; Urbanowicz, Andrzej ^[5]; Morselli, Marco ^[1]; Dang, Johnny ^[1]; Pellegrini, Matteo ^[1]; Paul, Ketema ^[1]; Bentolila, Laurent A. ^[4]; Fiala, Milan ^[1]

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1. UCLA School of Life Sciences, Los Angeles, CA (United States)
2. University of California SanDiego Health Sciences, La Jolla, CA (United States)
3. University of California, Davis, CA (United States)
4. University of California, Los Angeles, CA (United States)
5. Warsaw University of Technology (Poland)

Macrophages of healthy subjects have a pro-resolution phenotype, upload amyloid-β (Aβ) into endosomes, and degrade Aβ, whereas macrophages of patients with Alzheimer’s disease (AD) generally have a pro-inflammatory phenotype and lack energy for brain clearance of Aβ. To clarify the pathogenesis of sporadic AD and therapeutic effects of polyunsaturated fatty acids (PUFA) with vitamins B and D and antioxidants on monocyte/macrophage (MM) migration in the AD brain, MM transcripts in energy and Aβ degradation, MM glycome, and macrophage clearance of Aβ. We followed for 31.3 months (mean) ten PUFA-supplemented neurodegenerative patients: 3 with subjective cognitive impairment (SCI), 2 with mild cognitive impairment (MCI), 3 MCI/vascular cognitive impairment, 2 with dementia with Lewy bodies, and 7 non-supplemented caregivers. We examined: monocyte migration in the brain and a blood-brain barrier model by immunochemistry and electron microscopy; macrophage transcriptome by RNAseq; macrophage glycome by N-glycan profiling and LTQ-Orbitrap mass spectrometry; and macrophage phenotype and phagocytosis by immunofluorescence. MM invade Aβ plaques, upload but do not degrade Aβ, and release Aβ into vessels, which develop cerebrovascular amyloid angiopathy (CAA); PUFA upregulate energy and Aβ degradation enzyme transcripts in macrophages; PUFA enhance sialylated N-glycans in macrophages; PUFA reduce oxidative stress and increase pro-resolution MM phenotype, mitochondrial membrane potential, and Aβ phagocytosis (p < 0.001). Macrophages of SCI, MCI, and AD patients have interrelated defects in the transcriptome, glycome, Aβ phagocytosis, and Aβ degradation. PUFA mend macrophage transcriptome, enrich glycome, enhance Aβ clearance, and benefit the cognition of early-stage AD patients.

• Research Organization: University of California, Los Angeles, CA (United States)
• Sponsoring Organization: USDOE
• OSTI ID: 2424564
• Journal Information: Journal of Alzheimer's Disease, Journal Name: Journal of Alzheimer's Disease Journal Issue: 1 Vol. 91; ISSN 1387-2877
• Publisher: IOS Press
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
Alzheimer’s disease
Neurosciences &amp; Neurology
amyloid-β
cerebrovascular amyloid angiopathy
coenzyme Q2
glycome
macrophage
mitochondrial membrane potential
phagocytosis
polyunsaturated fatty acids
transcriptome