Microglial activation induced by factor(s) contained in sera from Alzheimer-related ApoE genotypes

Topic: Brain proteins, microglia and lab models

The risk of developing AD definitely increases with (a) age, (b) head injuries, (c) family history of AD or Down syndrome, (d) sex (higher prevalence of AD in women), (e) vascular disease, (f) exposure to environmental toxins, (g) infectious processes, or (h) changes in immune function, and recent advances in molecular genetics have suggested that genetic predisposition (i) can be considered one of the most important risk factors in the development of AD. A significant increase in the number of amyloid plaques in AD patients with an apolipoprotein E4 (ApoE) allele has been observed and the results of several genetic studies indicate that the etiology of this neurodegenerative disease is associated with the presence of the allele E4 of ApoE. A potential source of damage in the AD brain is an altered response triggered by microglial activation, which is associated with amyloid plaques. Many studies have shown that microglia secrete both cytokines and cytotoxins and since reactive microglia appears in nearly every type of brain damage, it is likely that their secreted products ultimately help to determine the rate of damaged brain tissue. Results show that a modulation in the proliferation and activation of microglial cells was obtained and that AD sera, mainly in the ApoE 3/4 and 4/4 genotype contain factor(s) which are able to induce morphological changes, as measured by an increase in the ameboid cell type. These results strongly suggest that primary in vitro microglial cell cultures can be used as a screening model to test human sera as well as the effect of new potential drugs aimed at down-regulating microglia activation.

Key findings

• The risk of developing AD definitely increases with (a) age, (b) head injuries, (c) family history of AD or Down syndrome, (d) sex (higher prevalence of AD in women), (e) vascular disease, (f) exposure to environmental toxins, (g) infectious processes, or (h) changes in immune function, and recent advances in molecular genetics have suggested that genetic predisposition (i) can be considered one of the most important risk factors in the development of AD.
• A significant increase in the number of amyloid plaques in AD patients with an apolipoprotein E4 (ApoE) allele has been observed and the results of several genetic studies indicate that the etiology of this neurodegenerative disease is associated with the presence of the allele E4 of ApoE.
• A potential source of damage in the AD brain is an altered response triggered by microglial activation, which is associated with amyloid plaques.
• Many studies have shown that microglia secrete both cytokines and cytotoxins and since reactive microglia appears in nearly every type of brain damage, it is likely that their secreted products ultimately help to determine the rate of damaged brain tissue.
• Results show that a modulation in the proliferation and activation of microglial cells was obtained and that AD sera, mainly in the ApoE 3/4 and 4/4 genotype contain factor(s) which are able to induce morphological changes, as measured by an increase in the ameboid cell type.

Why it matters

This laboratory study found that serum from people with certain ApoE genotypes, mainly ApoE 3/4 and 4/4, contained factors that changed microglial cell proliferation and activation. It suggests immune-related processes may play a role in Alzheimer's disease, but it does not test or identify any treatment.

Study details

• Effect size2.5%
• Evidence strengthLow

Read the original

• DOI: 10.1002/(sici)1097-4547(19981115)54:4<539::aid-jnr11>3.0.co;2-q
• PubMed: 9822164
• Original source →

May need a subscription OpenAlex found no free copy of the full text (checked 6 Feb 1020), so the publisher may charge for it. The PubMed abstract is free.

@article{lombardi1998-9822164,
  author  = {Lombardi, V. R. and García, M. and Cacabelos, R.},
  title   = {{Microglial activation induced by factor(s) contained in sera from Alzheimer-related ApoE genotypes}},
  journal = {Journal of neuroscience research},
  year    = {1998},
  doi     = {10.1002/(sici)1097-4547(19981115)54:4<539::aid-jnr11>3.0.co;2-q},
  pmid    = {9822164},
  url     = {https://doi.org/10.1002/(sici)1097-4547(19981115)54:4<539::aid-jnr11>3.0.co;2-q}
}

Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease Nature · 1995-06-01 · usefulness score 64/100 · Genetics
• Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease Nature · 1991-02-21 · usefulness score 63/100 · Genetics
• Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease Proceedings of the National Academy of Sciences of the United States of America · 1993-03-01 · usefulness score 58/100 · Genetics
• Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson's and Alzheimer's disease brains Neurology · 1988-08-01 · usefulness score 56/100 · Getting a diagnosis
• Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. Journal of Lipid Research · 1990-03-01 · usefulness score 53/100 · Genetics
• Cellular forms and functions of brain microglia Brain research bulletin · 1994-01-01 · usefulness score 41/100 · Inflammation and the immune system
• Measurement of amyloid peptide precursor of Alzheimer disease in human blood by double antibody immunoradiometric assay Alzheimer disease and associated disorders · 1991-01-01 · usefulness score 36/100 · Down syndrome and Alzheimer's

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• Microglial activation and amyloid deposition in mild cognitive impairment: a PET study Neurology · 2009-01-01 · usefulness score 53/100 · Inflammation and the immune system

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