Lennart Mucke, MD

Overview
Lennart Mucke’s laboratory aims to unravel how major neurologic and psychiatric conditions cause cognitive deficits, behavioral abnormalities, and other disabling symptoms, with an emphasis on dementias, epilepsy, and autism.

Our group uses mouse models and brain cell cultures to study disease-causing factors and pathways at molecular, cellular, network, and behavioral levels. Such models are also used to identify and validate novel entry points for therapeutic interventions.

The clinical relevance of discoveries is assessed through collaborative studies of human patients and brain tissues. Several findings we originally made in mouse models were subsequently identified for the first time in the human condition, highlighting the validity and power of experimental models. The most informative models have been used to identify novel strategies to counteract the development of brain dysfunctions and decline.

Major Contributions
• Instigated paradigm shifts in understanding and preventing the pathogenesis of Alzheimer’s disease

• Advanced the field from its traditional focus on morphological changes toward an understanding of Alzheimer’s disease at the synaptic and neural network level

• Defined molecular and cellular mechanisms underlying cognitive decline in Alzheimer’s disease

• Discovered unexpected links among Alzheimer’s disease, epilepsy and autism

• Identified novel therapeutic strategies and paved the path toward the development of tau-lowering therapeutics

• Provided critical guidance for the design of clinical trials aimed at reversing network hyperexcitability in Alzheimer’s disease

• Encouraged and enabled the translation of scientific discoveries into better treatments for brain diseases that are frequent, devastating, and costly to populations around the world

Interests and Ongoing Studies
• Mechanisms and treatment of dementia, epilepsy, and autism spectrum disorders

• Pathobiology of amyloid proteins, tau, apolipoprotein E, α-synuclein, TREM2, PTEN, and related signaling pathways

• Neural processes underlying important brain functions

• Role of glia in health and disease

• Dissection of complex neuropathogenic pathways in experimental models

• Development and (pre)clinical assessment of novel therapeutic strategies

• Establishment and guidance of interdisciplinary research programs