David M. Holtzman is an American physician-scientist known for his work exploring the biological mechanisms underlying neurodegeneration, with a focus on Alzheimer's disease.

Holtzman's lab is known for examining how apoE4 contributes to Alzheimer's disease as well as how sleep modulates amyloid beta in the brain.

[2] His postdoctoral research focused on developing mouse models of neonatal stroke and neurodegeneration as well as elucidating the role neurotrophins play in modulating neuronal activity.

[7] Holtzman's work has studied mechanisms by which apoE, amyloid beta, and tau metabolism are implicated in neurodegeneration in the context of Alzheimer's disease.

Holtzman and his former trainee, Randall Bateman, developed C2N Diagnostics in 2007 with the goal of increasing the understanding the molecular mechanisms underlying neurological diseases through measurements of concentration and metabolism of CNS-derived biomolecules.

[7] Holtzman's Lab has shown that apoE contributes to AD susceptibility and pathogenesis by its modulation of Aβ clearance and aggregation.

These findings suggest that increased metabolic demands and activity levels lead to higher soluble Aβ loads in these brain regions involved in the default mode network.