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Abstract Title:

A pilot study on the effect of lactoferrin on Alzheimer's disease pathological sequelae: Impact of the p-Akt/PTEN pathway.

Abstract Source:

Biomed Pharmacother. 2019 Mar ;111:714-723. Epub 2019 Jan 3. PMID: 30611996

Abstract Author(s):

Waleed A Mohamed, Rania M Salama, Mona F Schaalan

Article Affiliation:

Waleed A Mohamed

Abstract:

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases in which the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (PKB or Akt) pathway is deregulated in response to phosphatase and tensin homolog (PTEN) overexpression. Lactoferrin (LF), a multifunctional iron-binding glycoprotein, is involved in AD pathology; however, direct evidence of its impact upon AD remains unclear. To elucidate LF's role in AD, the possible protective mechanism post-LF administration for 3 months was investigated in AD patients by observing changes in the p-Akt/PTEN pathway. AD patients showed decreased serum acetylcholine (ACh), serotonin (5-HT), antioxidant and anti-inflammatory markers, and decreased expression of Akt in peripheral blood lymphocytes (PBL), as well as PI3K, and p-Akt levels in PBL lysate; all these parameters were significantly improved after daily LF administration for 3 months. Similarly, elevated serum amyloidβ (Aβ) 42, cholesterol, oxidative stress markers, IL-6, heat shock protein (HSP) 90, caspase-3, and p-tau, as well as increased expression of tau, MAPK1 and PTEN in AD patients, were significantly reduced upon LF intake. Improvement in the aforementioned AD surrogate markers post-LF treatment wasreflected in enhanced cognitive function assessed by the Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale-Cognitive Subscale 11-item (ADAS-COG 11) questionnaires as clinical endpoints. These results provide a basis for a possible protective mechanism of LF in AD throughits ability to alleviate the AD pathological cascade and cognitive decline via modulation of the p-Akt/PTEN pathway, which affects the key players of inflammation and oxidative stress that are involved in AD pathology.

Study Type : Human Study

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