Dena Dubal, MD, PhD

Assistant Professor
+1 415 502-7237

The goal of our research is to investigate mechanisms of longevity, resilience and neurodegenerative disease. Broadly we investigate how aging pathways can confer resilience to a brain and counter neurodegenerative diseases like Alzheimer’s. Using genetic mouse models, cell culture methods, and study of human populations using cutting-edge techniques, we study whether longevity-derived mechanisms can pave a path toward development of urgently needed therapies in aging and disease.

To this end, we are unraveling mechanisms that underlie female longevity, studying sex chromosomal contributions to neurodegenerative disease, and investigating the longevity hormone klotho in the normal and diseased brain.


Pathways to brain resilience.

Nature medicine

Dubal DB

KLOTHO heterozygosity attenuates APOE4-related amyloid burden in preclinical AD.


Erickson CM, Schultz SA, Oh JM, Darst BF, Ma Y, Norton D, Betthauser T, Gallagher CL, Carlsson CM, Bendlin BB, Asthana S, Hermann BP, Sager MA, Blennow K, Zetterberg H, Engelman CD, Christian BT, Johnson SC, Dubal DB, Okonkwo OC

Cognitive aging is not created equally: differentiating unique cognitive phenotypes in "normal" adults.

Neurobiology of aging

Casaletto KB, Elahi FM, Staffaroni AM, Walters S, Contreras WR, Wolf A, Dubal D, Miller B, Yaffe K, Kramer JH

Ovarian Cycle Stages Modulate Alzheimer-Related Cognitive and Brain Network Alterations in Female Mice.


Broestl L, Worden K, Moreno AJ, Davis EJ, Wang D, Garay B, Singh T, Verret L, Palop JJ, Dubal DB

The Way of Tau: Secretion and Synaptic Dysfunction.

Trends in molecular medicine

Dubal DB

Cord blood klotho levels are inversely associated with leptin in healthy Latino neonates at risk for obesity.

Journal of pediatric endocrinology & metabolism : JPEM

Wojcicki JM, Prather AA, Epel E, Wang D, Dubal DB

Peripheral Elevation of a Klotho Fragment Enhances Brain Function and Resilience in Young, Aging, and a-Synuclein Transgenic Mice.

Cell reports

Leon J, Moreno AJ, Garay BI, Chalkley RJ, Burlingame AL, Wang D, Dubal DB

BDNF Val66Met predicts cognitive decline in the Wisconsin Registry for Alzheimer's Prevention.


Boots EA, Schultz SA, Clark LR, Racine AM, Darst BF, Koscik RL, Carlsson CM, Gallagher CL, Hogan KJ, Bendlin BB, Asthana S, Sager MA, Hermann BP, Christian BT, Dubal DB, Engelman CD, Johnson SC, Okonkwo OC

Systemic klotho is associated with KLOTHO variation and predicts intrinsic cortical connectivity in healthy human aging.

Brain imaging and behavior

Yokoyama JS, Marx G, Brown JA, Bonham LW, Wang D, Coppola G, Seeley WW, Rosen HJ, Miller BL, Kramer JH, Dubal DB

Sex biology contributions to vulnerability to Alzheimer's disease: A think tank convened by the Women's Alzheimer's Research Initiative.

Alzheimer's & dementia : the journal of the Alzheimer's Association

Snyder HM, Asthana S, Bain L, Brinton R, Craft S, Dubal DB, Espeland MA, Gatz M, Mielke MM, Raber J, Rapp PR, Yaffe K, Carrillo MC

Network dysfunction in a-synuclein transgenic mice and human Lewy body dementia.

Annals of clinical and translational neurology

Morris M, Sanchez PE, Verret L, Beagle AJ, Guo W, Dubal D, Ranasinghe KG, Koyama A, Ho K, Yu GQ, Vossel KA, Mucke L

Longevity factor klotho and chronic psychological stress.

Translational psychiatry

Prather AA, Epel ES, Arenander J, Broestl L, Garay BI, Wang D, Dubal DB

Life extension factor klotho prevents mortality and enhances cognition in hAPP transgenic mice.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Dubal DB, Zhu L, Sanchez PE, Worden K, Broestl L, Johnson E, Ho K, Yu GQ, Kim D, Betourne A, Kuro-O M, Masliah E, Abraham CR, Mucke L

Astrocytic adenosine receptor A2A and Gs-coupled signaling regulate memory.

Nature neuroscience

Orr AG, Hsiao EC, Wang MM, Ho K, Kim DH, Wang X, Guo W, Kang J, Yu GQ, Adame A, Devidze N, Dubal DB, Masliah E, Conklin BR, Mucke L

Variation in longevity gene KLOTHO is associated with greater cortical volumes.

Annals of clinical and translational neurology

Yokoyama JS, Sturm VE, Bonham LW, Klein E, Arfanakis K, Yu L, Coppola G, Kramer JH, Bennett DA, Miller BL, Dubal DB

Life extension factor klotho enhances cognition.

Cell reports

Dubal DB, Yokoyama JS, Zhu L, Broestl L, Worden K, Wang D, Sturm VE, Kim D, Klein E, Yu GQ, Ho K, Eilertson KE, Yu L, Kuro-o M, De Jager PL, Coppola G, Small GW, Bennett DA, Kramer JH, Abraham CR, Miller BL, Mucke L

Reversible suppression of electrocerebral activity.

The Neurohospitalist

Broestl L, Cornes S, Dubal DB

T-cell lymphoproliferative disorder following mycophenolate treatment for myasthenia gravis.

Muscle & nerve

Dubal DB, Mueller S, Ruben BS, Engstrom JW, Josephson SA

Collagen VI protects neurons against Abeta toxicity.

Nature neuroscience

Cheng JS, Dubal DB, Kim DH, Legleiter J, Cheng IH, Yu GQ, Tesseur I, Wyss-Coray T, Bonaldo P, Mucke L

A case of paraneoplastic myelopathy associated with the neuromyelitis optica antibody.

Nature clinical practice. Neurology

Mueller S, Dubal DB, Josephson SA

Differential modulation of estrogen receptors (ERs) in ischemic brain injury: a role for ERalpha in estradiol-mediated protection against delayed cell death.


Dubal DB, Rau SW, Shughrue PJ, Zhu H, Yu J, Cashion AB, Suzuki S, Gerhold LM, Bottner MB, Dubal SB, Merchanthaler I, Kindy MS, Wise PM

Stroke injury in rats causes an increase in activin A gene expression which is unaffected by oestradiol treatment.

Journal of neuroendocrinology

Böttner M, Dubal DB, Rau SW, Suzuki S, Wise PM

Estradiol attenuates programmed cell death after stroke-like injury.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Rau SW, Dubal DB, Böttner M, Gerhold LM, Wise PM

Estradiol differentially regulates c-Fos after focal cerebral ischemia.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Rau SW, Dubal DB, Böttner M, Wise PM

Estrogen and neuroprotection: from clinical observations to molecular mechanisms.

Dialogues in clinical neuroscience

Dubal DB, Wise PM

Neuroendocrine modulation and repercussions of female reproductive aging.

Recent progress in hormone research

Wise PM, Smith MJ, Dubal DB, Wilson ME, Rau SW, Cashion AB, Böttner M, Rosewell KL

Estradiol is a protective factor in the adult and aging brain: understanding of mechanisms derived from in vivo and in vitro studies.

Brain research. Brain research reviews

Wise PM, Dubal DB, Wilson ME, Rau SW, Böttner M, Rosewell KL

Minireview: neuroprotective effects of estrogen-new insights into mechanisms of action.


Wise PM, Dubal DB, Wilson ME, Rau SW, Böttner M

Estrogen receptor alpha, not beta, is a critical link in estradiol-mediated protection against brain injury.

Proceedings of the National Academy of Sciences of the United States of America

Dubal DB, Zhu H, Yu J, Rau SW, Shughrue PJ, Merchenthaler I, Kindy MS, Wise PM

Estrogens: trophic and protective factors in the adult brain.

Frontiers in neuroendocrinology

Wise PM, Dubal DB, Wilson ME, Rau SW, Liu Y

Estradiol is a neuroprotective factor in in vivo and in vitro models of brain injury.

Journal of neurocytology

Wise PM, Dubal DB, Wilson ME, Rau SW

Estradiol: a protective and trophic factor in the brain.

Journal of Alzheimer's disease : JAD

Dubal DB, Wilson ME, Wise PM

Estradiol modulates bcl-2 in cerebral ischemia: a potential role for estrogen receptors.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Dubal DB, Shughrue PJ, Wilson ME, Merchenthaler I, Wise PM

Neuroendocrine influences and repercussions of the menopause.

Endocrine reviews

Wise PM, Smith MJ, Dubal DB, Wilson ME, Krajnak KM, Rosewell KL

Estradiol protects against ischemic injury.

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

Dubal DB, Kashon ML, Pettigrew LC, Ren JM, Finklestein SP, Rau SW, Wise PM