Heme Deficiency in Alzheimer’s Disease: A Possible Connection to Porphyria

Mechanisms that cause Alzheimer’s disease (AD), an invariablyfatal neurodegenerative disease, are unknown. Important recentdata indicate that neuronal heme deficiency maycontribute to AD pathogenesis. If true, factors that contribute tothe intracellular heme deficiency could potentially alter thecourse of AD. The porphyrias are metabolic disorders characterizedby enzyme deficiencies in the heme biosynthetic pathway. Wehypothesize that AD may differ significantly in individualspossessing the genetic trait for an acute hepatic porphyria. Weelaborate on this hypothesis and briefly review thecharacteristics of the acute hepatic porphyrias that may berelevant to AD. We note the proximity of genes encoding enzymes ofthe heme biosynthesis pathway to genetic loci linked to sporadic,late-onset AD. In addition, we suggest that identification ofindividuals carrying the genetic trait for acute porphyria mayprovide a unique resource for investigating AD pathogenesis andinform treatment and management decisions