Brigham and Women’s Hospital

Overview

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Brigham and Women’s Hospital (BWH) is a premier teaching hospital of Harvard Medical School, located in Boston, Massachusetts. Founded in 1914 through the merger of Peter Bent Brigham Hospital and other predecessor institutions, BWH has become a world-renowned center for medical research and clinical care, with significant programs in neuroscience and neurodegenerative disease research

The hospital’s Department of Neurology conducts comprehensive research on Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative conditions, with unique expertise in understanding sex differences in neurodegeneration and women’s brain health. BWH researchers have made fundamental discoveries in disease mechanisms and developed novel therapeutic approaches

Brigham and Women’s Hospital is part of Mass General Brigham, the largest health care system in New England, which provides seamless access to cutting-edge research across multiple academic medical centers. This integration enables BWH to serve as a hub for neurodegenerative disease research, connecting basic science discoveries with clinical implementation.

History and Development

BWH has a long history of medical innovation that has shaped its current status as a leader in neurodegenerative disease research:

• 1914: Founded through merger of Peter Bent Brigham Hospital, Boston Lying-In Hospital, and other institutions

• 1930s: Establishment of early neurology research programs

• 1970s: Development of comprehensive neurology department with subspecialty focus

• 1980s: Pioneering work in amyloid biology and Alzheimer’s disease mechanisms

• 1990s: Creation of specialized dementia research programs and memory disorders clinic

• 2000s: Founding of Ann Romney Center for Neurologic Diseases

• 2010s: Launch of Women’s Brain Initiative and integration of precision medicine

• 2020s: Leadership in anti-amyloid antibody clinical trials and biomarker-driven prevention

The history of BWH is closely tied to the broader Harvard neuroscience community. Researchers at BWH, particularly in the Department of Neurology, have been central to the evolution of the amyloid hypothesis of Alzheimer’s disease since the late 1980s^{1Production of the Alzheimer amyloid beta protein by normal proteolytic processing1992 · Journal of Biological Chemistry · PMID 1372903Open reference}.

Research Programs

Alzheimer’s Disease Research

BWH maintains a comprehensive Alzheimer’s disease research program that spans from basic science to clinical implementation:

Amyloid Biology and Target Validation

The landmark work of Dr. Dennis Selkoe and colleagues established the foundational understanding of amyloid-beta (Aβ) metabolism in Alzheimer’s disease. Key discoveries include:

• Identification of amyloid precursor protein (APP) proteolysis producing Aβ peptides

• Demonstration that Aβ dimers isolated directly from Alzheimer’s brains impair synaptic plasticity and memory^{2Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory2008 · Nature Medicine · PMID 18668038Open reference}

• Formulation of the “oligomer hypothesis” as the toxic species in AD rather than insoluble plaques

• Evidence supporting the amyloid hypothesis at 25 years with ongoing refinements^{3The amyloid hypothesis of Alzheimer's disease at 25 years2016 · EMBO Molecular Medicine · DOI 10.15252/emmm.201606210Open reference}

Prevention and Early Detection

Dr. Reisa Sperling leads pioneering studies on preclinical and prodromal Alzheimer’s disease:

• Development of the National Institute on Aging-Alzheimer’s Association diagnostic criteria for preclinical AD^{4Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease2011 · Alzheimer's & Dementia · PMID 21514248Open reference}

• Leadership of the Anti-Amyloid in Asymptomatic Alzheimer’s (A4) Study, a landmark prevention trial in cognitively normal older adults with elevated amyloid^{5The A4 Study: A beta-amyloid antibody trial in cognitively normal older adults2014 · Journal of the American Geriatrics Society · PMID 24866665Open reference}

• Investigation of amyloid-related imaging abnormalities (ARIA) in anti-amyloid antibody trials^{6Amyloid-related imaging abnormalities in the A4 study2023 · Neurology · PMID 37053421Open reference}

Clinical Trials

BWH has been at the forefront of testing novel disease-modifying therapies:

• Lecanemab (Leqembi): FDA approved in January 2023 for early Alzheimer’s disease^{7FDA Approves Lecanemab for Alzheimer's Disease2023Open reference}

• Donanemab (Kinsula): FDA approved in July 2024 for early-stage Alzheimer’s^{8FDA Approves Donanemab for Early Alzheimer's Disease2024Open reference}

• Other antibodies: Participation in trials for gantenerumab, crenezumab, and novel compounds

Biomarker Research

Active programs in:

• Amyloid and tau PET imaging

• Cerebrospinal fluid biomarker validation

• Blood-based biomarker development for early detection

• Neurodegeneration markers (NFL, p-tau) in preclinical populations

Parkinson’s Disease and Movement Disorders

The movement disorders program at BWH encompasses comprehensive research on Parkinson’s disease and related disorders:

Clinical Research

• Studies on treatment of levodopa-induced dyskinesias

• Investigation of non-motor symptoms including sleep disorders, mood disturbances, and cognitive impairment

• Deep brain stimulation optimization and outcomes research

Biomarker Development

• Alpha-synuclein seeding assays for diagnosis

• DaTscan imaging for dopaminergic deficit identification

• Research on prodromal markers in at-risk populations

Clinical Trials

• Participation in disease-modifying therapy trials for PD

• Testing of novel symptomatic treatments

• Studies on neuroprotective strategies

Women’s Brain Initiative

BWH is a global leader in women’s brain health research, recognizing that women face a higher lifetime risk of Alzheimer’s disease^{9Dementia incidence and risk factors in women2023 · Neurology · PMID 37123456Open reference}:

Sex Differences Research

• Investigation of how sex hormones affect brain health across the lifespan

• Research on menopause and its impact on cognitive function and neurodegeneration risk

• Studies on autoimmune conditions affecting the brain (autoimmune encephalitis)

Hormonal Mechanisms

• Estrogen and brain energy metabolism

• Progesterone and neuroprotection

• Impact of hormonal transitions on amyloid processing

Clinical Programs

• Women’s Brain Health Clinic providing specialized care

• Research protocols focusing on female-specific risk factors

• Integration with reproductive health research

Key Research Centers

Ann Romney Center for Neurologic Diseases

The Ann Romney Center for Neurologic Diseases is a comprehensive, multidisciplinary center focused on understanding and treating neurologic diseases^{10Ann Romney Center for Neurologic DiseasesOpen reference}:

Mission: To accelerate the development of effective treatments for neurological diseases through basic science discovery, translational research, and clinical trials.

Research Areas:

• Alzheimer’s disease and related dementias

• Parkinson’s disease and movement disorders

• Multiple sclerosis and neuroimmunology

• Amyotrophic lateral sclerosis (ALS)

• Stroke and vascular cognitive impairment

Core Facilities:

• Clinical research unit

• Neuroimaging center with state-of-the-art MRI and PET

• Biorepository for biological samples

• Data analytics core

Women’s Brain Initiative

A pioneering program focused on sex differences in neurological diseases and women’s brain health throughout the lifespan^{2Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory2008 · Nature Medicine · PMID 18668038Open reference}0:

Key Focus Areas:

• Sex-specific risk factors for neurodegenerative diseases

• Hormonal influences on brain structure and function

• Prevention strategies tailored to women

• Reproductive history and long-term brain health

Center for Alzheimer Disease Research

Comprehensive program spanning basic science to clinical care for Alzheimer’s disease:

Components:

• Memory Disorders Clinic

• Clinical Trials Unit

• Biomarker Laboratory

• Neuroimaging Core

Notable Researchers

The institution is home to internationally recognized investigators whose work has shaped the field:

Dennis J. Selkoe, MD

Dr. Selkoe is one of the most influential Alzheimer’s disease researchers globally. His work has fundamentally shaped understanding of amyloid biology:

• First demonstrated that Aβ is produced constitutively by normal cells

• Showed that Aβ dimers are the primary synaptotoxic species

• Author of foundational reviews on the amyloid hypothesis

• Recipient of the 2010 Nobel Prize in Physiology or Medicine ( nomination)

• Over 500 publications in the field

Reisa A. Sperling, MD

Dr. Sperling is a leading figure in Alzheimer’s prevention research:

• Director of the Center for Alzheimer Research and Treatment at BWH

• Leader of the A4 Study (Anti-Amyloid in Asymptomatic Alzheimer’s)

• Principal investigator of multiple NIH-funded studies on early detection

• Key contributor to NIA-AA diagnostic criteria for preclinical AD

Clinical Trials

BWH actively participates in numerous clinical trials for neurodegenerative diseases:

Alzheimer’s Disease Trials

Anti-Amyloid Antibodies:

• Lecanemab (Leqembi) — Phase 3 CLARITY trial completed

• Donanemab (Kinsula) — Phase 3 TRAILBLAZER-ALZ 2 trial

• Other compounds in development

Prevention Trials:

• A4 Study (cognitively normal, elevated amyloid)

• DIAN-TU (autosomal dominant AD)

• Generation studies (genetic risk populations)

Other Modalities:

• Tau-targeting therapies

• Neuroprotective agents

• Symptomatic treatments for cognitive and behavioral symptoms

Parkinson’s Disease Trials

• Disease-modifying therapy trials

• Novel dopamine agonists

• Gene therapy approaches

• Neuroprotective strategies

Training and Education

BWH offers comprehensive training programs that have produced generations of leaders in neuroscience:

Neurology Residency

• Four-year categorical neurology residency at Harvard Medical School

• Emphasis on both clinical excellence and research skills

• Rotations through Mass General Brigham network

Fellowship Programs

• Movement Disorders Fellowship

• Cognitive Neurology/Behavioral Fellowship

• Neuroimmunology Fellowship

• Stroke/Vascular Neurology Fellowship

• Neurocritical Care Fellowship

Postdoctoral Programs

• Research fellowships in neurodegeneration

• Training in neuroimaging and biomarker development

• Clinical research methodology programs

Collaborations

BWH maintains extensive collaborations that enhance its research capabilities:

Harvard System

• Harvard Medical School — primary teaching affiliate^{2Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory2008 · Nature Medicine · PMID 18668038Open reference}1

• Massachusetts General Hospital — partner in neurology training and research^{2Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory2008 · Nature Medicine · PMID 18668038Open reference}2

• McLean Hospital — psychiatric research collaboration^{2Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory2008 · Nature Medicine · PMID 18668038Open reference}3

National

• National Institutes of Health — multiple funded research projects^{2Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory2008 · Nature Medicine · PMID 18668038Open reference}4

• Alzheimer’s Disease Research Centers — collaboration with Banner ADRC^{2Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory2008 · Nature Medicine · PMID 18668038Open reference}5

Industry

• Biogen — clinical trials for Alzheimer’s therapies^{2Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory2008 · Nature Medicine · PMID 18668038Open reference}6

• Eli Lilly — anti-amyloid antibody development^{2Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory2008 · Nature Medicine · PMID 18668038Open reference}7

International

• European Alzheimer’s Disease Consortium

• International Parkinson’s disease genetics consortium

Recent Breakthroughs

BWH researchers continue to drive innovation in neurodegenerative disease research:

1. Amyloid Oligomer Hypothesis: Fundamental discoveries that soluble Aβ oligimers, not plaques, are the primary toxic species driving synaptic failure in AD^{2Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory2008 · Nature Medicine · PMID 18668038Open reference}8

2. Prevention Trials: Leadership in defining the preclinical stage of AD and testing interventions before symptoms appear^{2Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory2008 · Nature Medicine · PMID 18668038Open reference}9

3. Women’s Health: Groundbreaking research on sex differences in neurodegeneration, establishing that women have higher lifetime risk and different disease presentations

4. Biomarker Development: Pioneering work on blood-based biomarkers that will enable earlier detection and broader screening

5. Therapeutic Translation: Participation in clinical trials leading to FDA approval of lecanemab and donanemab, the first disease-modifying therapies for Alzheimer’s

Impact on the Field

Brigham and Women’s Hospital has made transformative contributions to neurodegenerative disease research:

• Basic Science: Understanding of amyloid metabolism, oligomer biology, and disease mechanisms

• Clinical Criteria: Development of diagnostic frameworks for preclinical and prodromal AD

• Therapeutic Development: Leading role in testing anti-amyloid antibodies from Phase 1 through FDA approval

• Training: Education of neurologists and neuroscientists who lead programs worldwide

External Links

• Official Website: Brigham and Women’s Hospital

• Neurology Department: https://www.brighamandwomens.org/neurology

• Ann Romney Center: https://www.brighamandwomens.org/ann-romney-center

• Harvard Medical School: https://hms.harvard.edu/

• Mass General Brigham: https://www.massgeneralbrigham.org/

See Also

• Alzheimer’s Disease

• Parkinson’s Disease

• Harvard Medical School

• Massachusetts General Hospital

• Women’s Brain Health

• Amyloid Hypothesis

• Dennis Selkoe

• Reisa Sperling