Downsizing of lean body mass is a key determinant of Alzheimer's disease.
Lean body mass (LBM) encompasses all metabolically active organs distributed into visceral and structural tissue compartments and collecting the bulk of N and K stores of the human body. Transthyretin (TTR) is a plasma protein mainly secreted by the liver within a trimolecular TTR-RBP-retinol complex revealing from birth to old age strikingly similar evolutionary patterns with LBM in health and disease. TTR is also synthesized by the choroid plexus along distinct regulatory pathways. Chronic dietary methionine (Met) deprivation or cytokine-induced inflammatory disorders generates LBM downsizing following differentiated physiopathological processes. Met-restricted regimens downregulate the transsulfuration cascade causing upstream elevation of homocysteine (Hcy) safeguarding Met homeostasis and downstream drop of hydrogen sulfide (H2S) impairing anti-oxidative capacities. Elderly persons constitute a vulnerable population group exposed to increasing Hcy burden and declining H2S protection, notably in plant-eating communities or in the course of inflammatory illnesses. Appropriate correction of defective protein status and eradication of inflammatory processes may restore an appropriate LBM size allowing the hepatic production of the retinol circulating complex to resume, in contrast with the refractory choroidal TTR secretory process. As a result of improved health status, augmented concentrations of plasma-derived TTR and retinol may reach the cerebrospinal fluid and dismantle senile amyloid plaques, contributing to the prevention or the delay of the onset of neurodegenerative events in elderly subjects at risk of Alzheimer's disease.
Laboratory of Nutrition, Faculty of Pharmacy, University Louis Pasteur, Strasbourg, France.
Yves
Y
Ingenbleek
Laboratory of Clinical Pathology, New York Methodist Hospital, Weill-Cornell University, New York, NY, USA.
Larry H
LH
Bernstein
D000544:Alzheimer Disease / Q000175:diagnosis* / Q000378:metabolism*; D015992:Body Mass Index; D002831:Choroid Plexus / Q000378:metabolism; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism; D011228:Prealbumin / Q000378:metabolism*; D014801:Vitamin A / Q000378:metabolism
D011228:Prealbumin; D014801:Vitamin A; D006862:Hydrogen Sulfide
Alzheimer's disease; homocysteine; hydrogen sulfide; lean body mass; nutritional assessment; retinoids; transthyretin