Protein restriction cycles reduce IGF-1 and phosphorylated Tau and improve behavior in Alzheimer’s mice

A recent University of Southern California study showed great benefit in cycling intake of dietary protein — well, not all protein, but essential amino acids — in mice with Alzheimer’s disease.

The protein restriction cycles improved memory and reduced brain levels of phosphorylated tau in the mice, but did not affect brain levels of β amyloid (Aβ) plaques.

The protein cycles lasted four months and consisted of alternating weeks of a normal diet and a protein-restricted (PR) diet.

The normal diet contained 25% protein, 17% fat, and 58% carbohydrate.

The PR diet lacked nine essential amino acids (EAA) – that is, amino acids the body cannot make: isoleucine, leucine, lysine, methionine, phenyalanine, threonine, tryptophan, valine, and arginine. Fat and carbohydrate contents were presumably the same as in the normal diet.

Interestingly, the researchers supplemented the PR diet by adding more of the remaining 11 amino acids, mainly the nonessential amino acids (NEAA), to make the diet’s nitrogen content the same as in the normal control diet. As a result, the PR diet contained about twice the amount of NEAA as did the normal diet.

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An autophagic role in Alzheimer’s disease for intermittent dietary periods of very low-protein, high-carbohydrate intake

Here’s the text of an abstract I’ll be presenting at the European Molecular Biology Organization (EMBO) autophagy conference in Norway in May 2013:


Occasional periods of very low-protein, high-carbohydrate dietary intake may enhance lysosomal proteolysis in Alzheimer’s disease (AD) by increasing activity of transcription factor EB (TFEB) via inhibition of glycogen synthase kinase 3 (GSK3).

AD is characterized by 1) activation of neuronal autophagy with defective autolysosomal degradation, and 2) neuronal insulin resistance, characterized by increased amyloid-β (Aβ) production in autophagosomes and reduced neuronal internalization of extracellular Aβ oligomers.

Suitable AD therapies may therefore aim to reduce neuronal insulin resistance and increase activity of TFEB, a master gene regulator of lysosomal biogenesis. Upon cellular starvation and in response to inhibition of mammalian target of rapamycin (mTOR), TFEB translocates from the cytosol to the nucleus, whereupon it increases transcription of 291 genes, including many involved in autophagy. At least 20 of these genes participate in lysosomal biogenesis, acidification, and proteolysis.

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