In pursuit of brain resilience

In this research roundup, we look back on some of the ways Knight Initiative scientists have been pursuing ways to keep our minds sharp well into old age

Two groups of researchers, doctors with a patient, and a red and blue stained image of brain cells in two-by-two array.

May 12 2026

Only one in about 10,000 people will reach age 100 cognitively unscathed. Since 2022, the Phil and Penny Knight Initiative for Brain Resilience at Stanford’s Wu Tsai Neurosciences Institute has been working to understand what makes that kind of longevity possible—and what could be done to extend it to more people.

Knight Initiative research defies boundaries. Scientists supported by the initiative analyze “natural experiments” in public health to understand beneficial effects of vaccines on brain aging, investigate the inner workings of cells’ recycling centers to understand the origins of neurodegeneration, and study short-lived fish to understand the trajectory of natural aging. They frequently collaborate with researchers across wide-ranging research disciplines and departmental boundaries.

But broadly speaking, brain resilience research focuses on three key questions: What’s the link between the biology of aging and the risk of neurodegenerative disease? What makes some brains more resilient than others in the face of similar genetic or environmental stress? And how might we intervene to enhance resilience and treat or even prevent diseases like Alzheimer’s, Parkinson’s, and ALS?

Below, we’ve compiled some of the Knight Initiative research we’ve reported on in the Initiative’s first four years that best reflects these core intellectual themes and their potential impact on the science of brain resilience.

A New Science of Aging and Neurodegeneration

Changes in brain’s ‘sugar shield’ could be key to understanding effects of aging

Feb 26 2005

New findings about the sugary armor on the brain’s frontline cells could shed light on cognitive decline and diseases like Alzheimer’s and open new avenues for treatment

Watercolor image of a brain that explores the complex interplay between brain structures, neural networks, and lipid droplets, tied to Alzheimer's research and the APOE4/4 gene discovery.

Alzheimer’s risk gene tied to fatty blobs in brain’s immune cells

Mar 20 2024

Could lipid droplets in microglia tie together the many threads of Alzheimer’s biology?

Image of post-mortem human frontal cortex showing TREM1 (red stain) in microglia and macrophages (Iba1; green stain) surrounding pathological amyloid buildup (X34; blue stain). The amount of TREM1 observed postmortem correlated with disease severity in Alzheimer’s patients.

Research links age-related inflammation, microglia and Alzheimer’s Disease

Mar 27 2024

Pro-inflammatory protein TREM1 in peripheral immune cells may promote age-related cognitive decline and dementia, according to Knight Initiative–funded research

A neuron outlined in blue with purple dots indicating amyloid beta 42. — Courtesy Ching-Chieh Chou

Alzheimer’s may stem from breakdown of “recycling centers” in aging cells

Aug 18 2025

Knight Initiative researchers used a new lab model of aging human neurons to show that as cells age, lysosomes fall into disrepair and waste builds up—feeding a damaging cycle that could lead to Alzheimer’s

A microscope image showing molecules in red, blue, and cyan. — Courtesy Carla Shatz

Building bridges between Alzheimer’s theories

Sep 15 2025

A new study finds links between two popular models of the disease – and the results could change how researchers think about treatment

AI generated watercolor image of a brain.

Alzheimer’s and Parkinson’s biomarkers show promise for early diagnosis

Mar 19 2024

Two new studies supported by the Knight Initiative highlight groundbreaking new early biomarkers for the diagnosis and treatment of neurodegenerative disease

Several dozen simple figures of people in gray, blue, and purple. — Courtesy Ted Wilson

Parkinson’s comes in many forms. New biomarkers may explain why

Aug 13 2025

Blood and cerebrospinal fluid markers tied to inflammation and metabolism sort some patients into subgroups, according to Knight Initiative researchers, a step toward predicting progression and tailoring care

Promoting Brain Resilience

Blood Cells Mutated in Old Age Protect Against Alzheimer’s Disease

Aug 24 2023

Pathologist Siddhartha Jaiswal discovers a surprising twist to our biology: Age-related mutations that increase the risk of blood disease also protect against brain disease

Amyloid plaque burden image generated by DALL-E

Knight-funded research uncovers gene mutations that may prevent Alzheimer’s Disease

Feb 22 2024

Disabling the notorious APOE4 gene might protect against the disease, according to data from a massive genetic dataset

Illustration of people being rejuvenated in a fountain of youth that is shaped like a neuron — Tobias Wuestefeld

Alzheimer's "resilience signature" predicts who will develop dementia – and how fast

May 14 2025

Knight Initiative researchers discover a biomarker in spinal fluid that could help forecast Alzheimer’s progression and improve clinical trials

Debbie Styles smiles with her surgical team. Standing, from left to right: Tiffany, a research coordinator for the CARDIAC-PND Study, Dr. Martin Angst, and Dr. Igor Feinstein. — Photo courtesy Rhee Bevere

Under the Lights: What Surgery Reveals About Brain Resilience

Jun 4 2025

A team at Stanford, supported by the Knight Initiative for Brain Resilience, is using the biology of recovery to uncover why some aging brains withstand stress while others quietly unravel

Ravi Nath and Claire Bedbrook stand in an aisle of shelves filled with fish tanks. — Andrew Brodhead

Watching a lifetime in motion reveals the architecture of aging

Mar 12 2026

Knight Initiative scientists tracked every moment of the life of the African turquoise killifish, showing that behavior alone can forecast whether an animal will live a long or short life

Microscopy image with blue nuclear stain on black background and artistic rendition of cell proximity effects in red and green — Illustration courtesy Eric Sun

Blight or Benefit: How Cellular Neighbors Shape the Aging Brain

Dec 19 2024

Researchers at Stanford’s Knight Initiative for Brain Resilience merge spatial transcriptomics and AI to uncover how local cellular interactions drive brain aging and resilience