Table 1.

Correlation between metabolic alterations and clinical features in Alzheimer disease (AD) and Parkinson disease (PD).

Clinical Features	Metabolic Alterations	Pathologies
Vulnerability of hippocampus, lateral and medial temporal lobes, and posterior cingulate/precuneus Reduction in neuronal and synaptic activity Atrophy of the cortical regions Axonal damage Neurodegeneration	Glucose hypometabolism Aerobic glycolysis reduction Elevated levels of lactate and pyruvate Impairment of lactate shuttle Aβ oligomer accumulation Insulin resistance Reduced number of GLUTs Reduced TCA cycle metabolism Reduced activity of the ETC complexes Downregulation of IDH PPP impairment Altered GSH/GSSG ratio Oxidative stress Oxydated GLT1 and GS Glutamate excitotoxicity	AD, PD
Cognitive decline Dementia Impaired neurotransmission	Glucose hypometabolism Aβ oligomer accumulation Insulin resistance Reduced TCA cycle metabolism Reduced activity of the ETC complexes Oxidative stress Reduced Blood BCAAs Affected glutamate synthesis Decreased levels of glutamine Oxydated GLT1 and GS Glutamate excitotoxicity	AD
Insulin desensitization Brain insulin resistance	Glucose hypometabolism Abnormalities in mitochondrial structure and function Aβ oligomer accumulation Secretion of pro-inflammatory cytokines (TNF-α) Oxidative stress Energy deficiency	AD, PD
Chronic inflammation	Downregulation of BDNF and NGF Oxidative stress	AD, PD
Synaptic spine deterioration BBB disfunction	Aβ oligomer accumulation Reduction in the number of plasma membrane insulin receptors Complex IV dysfunction Oxidative stress	AD
Death of dopaminergic neurons Neurodegeneration	Decline of insulin receptors Hyperinsulinemia Insulin resistance GLT1 downregulation Glutamate excitotoxicity Downregulation of metabolism of glycine, serine, and threonine Ornithine and proline accumulation Altered collagen homeostasis	PD
Cell death	Inactivation of PKM2 Downregulation of the Wnt/β-catenin pathway Complex I dysfunction Oxidative stress ATP deficiency	AD, PD
α-Synuclein (α-syn) aggregation	Glucose hypometabolism GAPDH oxydation Abnormalities in mitochondrial structure and function Complex I dysfunction Oxidative stress Reduced ΔΨm	PD
Neurological deficits Hemolytic anemia Myopathy Locomotive defects Loss of DA neurons	Reduced TCA cycle metabolism Accumulation of citrate and 2-OG Epigenetic regulation modifications Deficiency of PGK activity Defective ATP production Defective dopamine production	PD
White matter degeneration Demyelination	Bioenergetic shift from glucose toward ketones Preserved metabolism of ketones Decreased MCT1 expression in the BBB Decline in mitochondrial respiration Oxidative stress Catabolism of myelin lipids into fatty acids to produce ketone bodies	AD, PD