Elena Biffi , Zachary Turple, Jessica Chung, Alessandro Biffi
Retinal biomarkers of Cerebral Small Vessel Disease: A systematic review
April 14, 2022
This research sought to conduct a systematic review of the role of retinal biomarkers in diagnosis and characterization of Cerebral Small Vessel Disease (CSVD).

Ning S, Jorfi M, Patel SR, Kim DY, Tanzi RE.
Neurotechnological Approaches to the Diagnosis and Treatment of Alzheimer's Disease. 
Mar. 24, 2022
This is a comprehensive review of emerging neurotechnologies for diagnosing and treating Alzheimer’s disease.

Prokopenko D, Lee S, Hecker J, Mullin K, Morgan S, Katsumata Y; Alzheimer’s Disease Neuroimaging Initiative (ADNI), Weiner MW, Fardo DW, Laird N, Bertram L, Hide W, Lange C, Tanzi RE.
Region-based analysis of rare genomic variants in whole-genome sequencing datasets reveal two novel Alzheimer's disease-associated genes: DTNB and DLG2. 
March 4, 2022
This paper also reports the first use of whole genome sequencing to identify Alzheimer’s disease-associated genes harboring rare genomic variants that increase risk for Alzheimer’s disease.

Sabbagh MN, Perez A, Holland TM, Boustani M, Peabody SR, Yaffe K, Bruno M, Paulsen R, O'Brien K, Wahid N, Tanzi RE. 
Primary prevention recommendations to reduce the risk of cognitive decline.
Jan. 13, 2022
This review provides a comprehensive list of  lifestyle interventions for reducing risk of cognitive decline and Alzheimer’s disease with age.

Noor Adra, Haoqi Sun, Wolfgang Ganglberger, Elissa M Ye, Lisa W Dümmer, Ryan A Tesh, Mike Westmeijer, Madalena Da Silva Cardoso, Erin Kitchener, An Ouyang, Joel Salinas, Jonathan Rosand, Sydney S Cash, Robert J Thomas, M Brandon Westover
Optimal Spindle Detection Parameters for Predicting Cognitive Performance
January 4, 2022
Sleep spindles, bursts of brain activity that occur during sleep, relate to cognitive function and can be measured through automated methods. Researchers have characterized how spindle detection parameter settings influence the association between spindles and cognition, and they identified parameters that best correlate with cognitive performance.

Christiane Wrann, DVM, PhD, Se Hoon Choi, PhD, Rudy Tanzi, PhD et al
Exercise hormone irisin is a critical regulator of cognitive function
August 20, 2021
For the first time scientists have shown that irisin, the cleaved and circulating form of the exercise-induced membrane protein FNDC5, is sufficient to confer the benefits of exercise on cognitive function. Learn more from our press release and news coverage of the study.

Rudy Tanzi, PhD, Filip K. Swirski, PhD et al
Astrocytic interleukin-3 programs microglia and limits Alzheimer’s disease
July 14, 2021
The researchers identified a signaling molecule that may help prevent Alzheimer’s; Interleukin-3 may reprogram immune responses in the brain that cause cell death and lead to dementia.

Yang H-S, Zhang C, Carlyle BC, Zhen SY, Trombetta BA,  Schultz AP, Pruzin JJ, Fitzpatrick CD,  Yau W-Y, Kirn DR, Rentz DM, Arnold SE, Johnson KA, Sperling RA, Chhatwal JP, Tanzi RE.
Plasma IL-12/IFN-g axis predicts cognitive trajectories in cognitively unimpaired older adults. 
June 23, 2021
This study describes two new blood-based biomarkers (identified by the McCance Center biomarker team),  which are indicative of brain health and cognitive trajectory with advancing age.

Rynearson KD, Ponnusamy M, Prikhodko O, Xie Y, Zhang C, Nguyen P, Hug B, Sawa M, Becker A, Spencer B, Florio J, Mante M, Salehi B, Arias C, Galasko D, Head BP, Johnson G, Lin JH, Duddy SK, Rissman RA, Mobley WC, Thinakaran G, Tanzi RE, Wagner SL.
Preclinical validation of a potent γ-secretase modulator for Alzheimer's disease prevention. 
April 5, 2021
This study describes a highly promising new drug (gamma secretase modulator) for lowering amyloid beta as a way to prevent and treat Alzheimer’s disease. The first clinical trial of the drug, being developed in the Tanzi lab, is slated for late 2022/early 2023.

Prokopenko D, Morgan SL, Mullin K, Hofmann O, Chapman B, Kirchner R; Alzheimer's Disease Neuroimaging Initiative (ADNI), Amberkar S, Wohlers I, Lange C, Hide W, Bertram L, Tanzi RE.
Whole-genome sequencing reveals new Alzheimer's disease-associated rare variants in loci related to synaptic function and neuronal development.
April 2, 2021
This paper reports the first use of whole genome sequencing to identify Alzheimer’s disease-associated genes harboring rare genomic variants that increase risk for Alzheimer’s disease.

Griciuc A, Tanzi RE.
The role of innate immune genes in Alzheimer's disease. 
Feb. 3, 2021
This a comprehensive review of Alzheimer’s disease-associated genes that control neuroinflammation in the brain, including the first one, CD33, identified by the Tanzi lab in 2008.

Diagram from paper
PDE3A Diagram: Click to enlarge

Christopher D. Anderson, MD, MMSc, FAAN
Influence of Genetic Variation in PDE3A on Endothelial Function and Stroke
December 23, 2019
We aimed to characterize the genetics of endothelial function and how this influences risk for cardiovascular diseases such as ischemic stroke.

Christopher D. Anderson, MD, MMSc, FAAN, Jonathan Rosand, MD
Regional brain atrophy in professional fighters: Different patterns, different mechanisms?

December 23, 2019
Concussive and subconcussive closed head injury due to repetitive blast or impact trauma represents the most common form of traumatic brain injury (TBI). A subset of this repetitive trauma population goes on to develop chronic traumatic encephalopathy (CTE), characterized by distinct neuropathologic features as well as cognitive, emotional, and behavioral changes. To date, the inciting mechanisms and injury features that predict CTE remain unclear.

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Resilience Diagram: Click to enlarge

Ana-Maria Vranceanu, PhD, Jonathan Rosand, MD
Baseline resilience and depression symptoms predict trajectory of depression in dyads of patients and their informal caregivers following discharge from the Neuro-ICU
December 19, 2019
To explore the impact of resiliency factors on the longitudinal trajectory of depressive symptoms in patients admitted to the Neuroscience Intensive Care Unit (Neuro-ICU) and their family caregivers.

Christopher D. Anderson, MD, MMSc, FAAN, Jonathan Rosand, MD
Associations of Radiographic Cerebral Small Vessel Disease with Acute Intracerebral Hemorrhage Volume, Hematoma Expansion, and Intraventricular Hemorrhage
December 16, 2019
The aim of this study was to evaluate the impact of radiographic cerebral small vessel disease (CSVD) on the severity of acute intracerebral hemorrhage (ICH) as measured by: ICH volume, hematoma expansion, and extension of intraventricular hemorrhage (IVH).

Jonathan Rosand, MD
Racial/ethnic disparities in the risk of intracerebral hemorrhage recurrence
December 12, 2019
To estimate the risk of intracerebral hemorrhage (ICH) recurrence in a large, diverse, US-based population and to identify racial/ethnic and socioeconomic subgroups at higher risk.

Rudolph Tanzi, PhD
Stratifying risk for dementia onset using large-scale electronic health record data: a retrospective cohort study
December 11, 2019
Preventing dementia, or modifying disease course, requires identification of presymptomatic or minimally symptomatic high-risk individuals. We used longitudinal electronic health records from two large academic medical centers and applied a validated natural language processing tool to estimate cognitive symptomatology. We used survival analysis to examine the association of cognitive symptoms with incident dementia diagnosis during up to 8 years of follow-up.

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Teeth Diagram: Click to enlarge

Erin Dunn, ScD, MPH
Teeth as Potential New Tools to Measure Early-Life Adversity and Subsequent Mental Health Risk: An Interdisciplinary Review and Conceptual Model
December 11, 2019
Early-life adversity affects nearly half of all youths in the United States and is a known risk factor for psychiatric disorders across the life course. One strategy to prevent mental illness may be to target interventions toward children who are exposed to adversity, particularly during sensitive periods when these adversities may have even more enduring effects. However, a major obstacle impeding progress in this area is the lack of tools to reliably and validly measure the existence and timing of early-life adversity. In this review, we summarize empirical work across dentistry, anthropology, and archaeology on human tooth development and discuss how teeth preserve a time-resolved record of our life experiences.

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Cromolyn Sodium Diagram: Click to enlarge

Rudolph Tanzi, PhD
Cromolyn sodium delays disease onset and is neuroprotective in the SOD1G93A Mouse Model of amyotrophic lateral sclerosis
November 27, 2019

Accumulating evidence suggests that neuroinflammatory processes are implicated in the initiation and progression of amyotrophic lateral sclerosis (ALS). Previous reports have demonstrated an increase in microgliosis and astrogliosis in the lumbar spinal cord of SOD1G93A transgenic mice before the onset of symptoms, a neuroinflammatory response which correlated with disease progression. Importantly, early stage homeostatic microglia enhanced motor neuron survival, while pro-inflammatory microglia were toxic to motor neurons in the SOD1G93A mice. Recent studies from our group have demonstrated that cromolyn sodium, an FDA approved compound, exerts neuroprotective effects in mouse models of Alzheimer’s disease by altering microglial cell activation. Here, we tested the neuroprotective and anti-inflammatory effects of cromolyn sodium in the SOD1G93A mouse model of ALS.

Can (Martin) Zhang, MD, PhD, Rudolph Tanzi, PhD
A Curcumin Analog Reduces Levels of the Alzheimer’s Disease-Associated Amyloid-β Protein by Modulating AβPP Processing and Autophagy
November 26, 2019
Recently, we reported the development of curcumin analogs and identified a lead compound, curcumin-like compound-R17 (CLC-R17), that significantly attenuates Aβ deposition in an AD transgenic mouse model. Here, we elucidated the mechanisms of this analog on Aβ levels and AβPP processing using cell models of AD. Using biochemical methods and our recently developed nanoplasmonic fiber tip probe technology, we showed that the lead compound potently lowers Aβ levels in conditioned media and reduces oligomeric amyloid levels in the cells.

Christopher D. Anderson, MD, MMSc, FAAN, Jonathan Rosand, MD
Genetics of Cerebral Small Vessel Disease
November 22, 2019
We aim to provide the reader with an overview of the genes and corresponding biological pathways that have been found to be implicated in rare and common forms of SVD.

Rudolph Tanzi, PhD, Can (Martin) Zhang, MD, PhD
Significant Upregulation of Alzheimer’s β-Amyloid Levels in a Living System Induced by Extracellular Elastin Polypeptides
November 4, 2019
Alzheimer’s disease (AD) is a neurodegenerative disorder and the primary cause of age-related dementia. The etiology of AD is complex and has not been completely elucidated. Herein, we report that treatment with elastin-like polypeptides (ELPs), a component of the brain extracellular matrix (ECM), significantly increased the levels of AD-related amyloid-β peptides (Aβ) both in vitro and in vivo.

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IgG Receptor Diagram: Click to enlarge

Can (Martin) Zhang, MD, PhD
The high-affinity IgG receptor FcγRI modulates peripheral nerve injury-induced neuropathic pain in rats
October 22, 2019
We aimed to investigate the impacts of FcγRI in neuropathic pain through pain-related neurobehavioral studies and underlying mechanisms by biochemical methods in animal and cell models.

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Hepatic apoE Diagram: Click to enlarge

Rudolph Tanzi, PhD
Lack of hepatic apoE does not influence early Aβ deposition: observations from a new APOE knock-in model
October 17, 2019
The apolipoprotein E (APOE) gene is the strongest genetic risk factor for late-onset Alzheimer disease (AD). ApoE is produced by both astrocytes and microglia in the brain, whereas hepatocytes produce the majority of apoE found in the periphery. Studies using APOE knock-in and transgenic mice have demonstrated a strong isoform-dependent effect of apoE on the accumulation of amyloid-β (Aβ) deposition in the brain in the form of both Aβ-containing amyloid plaques and cerebral amyloid angiopathy. However, the specific contributions of different apoE pools to AD pathogenesis remain unknown.

Diagram from paper
Blood-brain Barrier Diagram: Click to enlarge

Se Hoon Choi, PhD, Rudolph Tanzi, PhD
Blood-Brain Barrier Dysfunction in a 3D In Vitro Model of Alzheimer’s Disease
October 16, 2019
Harmful materials in the blood are prevented from entering the healthy brain by a highly selective blood-brain barrier (BBB), and impairment of barrier function has been associated with a variety of neurological diseases. In Alzheimer’s disease (AD), BBB breakdown has been shown to occur even before cognitive decline and brain pathology. To investigate the role of the cerebral vasculature in AD, a physiologically relevant 3D human neural cell culture microfluidic model is developed having a brain endothelial cell monolayer with a BBB-like phenotype.

This model is shown to recapitulate several key aspects of BBB dysfunction observed in AD patients: increased BBB permeability, decreased expression of claudin-1, claudin-5, and VE-cadherin, increased expression of matrix-metalloproteinase-2 and reactive oxygen species, and deposition of β-amyloid (Aβ) peptides at the vascular endothelium. Thus, it provides a well-controlled platform for investigating BBB function as well as for screening of new drugs that need to pass the BBB to gain access to neural tissues.

Joel Salinas, MD, MBA, MSc
Social health and brain health: Do neurologists also have a duty to treat social ills?
October 2, 2019
Understanding how social determinants influence brain health is crucial to inform public policy, identify high-risk individuals for cost-effective risk reduction, and improve population health interventions so all persons can thrive. But details of social determinants in neurologic conditions remain unclear and, compounding the complexity, these conditions change alongside social, political, and economic circumstances.

Shaun Patel, PhD
Caudate stimulation enhances learning
October 1, 2019
Neuromodulation is a promising treatment modality for disorders of learning and memory, offering the possibility of precise alteration of disordered neural circuits. Studies to date have failed to identify an optimal target and stimulation paradigm. We recorded local field potentials from implanted electrodes while subjects participated in an associative learning task requiring them to learn an association between presented images and a button press. Both caudate and dorsolateral prefrontal cortex demonstrated a beta power increase during the feedback period of the learning task that was greater following correct than incorrect trials. In dorsolateral prefrontal cortex, this difference increased with learning and persisted beyond the end of the feedback period. Caudate stimulation was associated with increased dorsolateral prefrontal cortex beta power following feedback. These findings suggest that temporally specific caudate stimulation is a promising neuromodulation strategy to improve learning in disorders of learning and memory.

Can (Martin) Zhang, MD, PhD
Gestational B-vitamin supplementation alleviates PM2.5-induced autism-like behavior and hippocampal neurodevelopmental impairment in mice offspring
September 20, 2019
Our results suggest that B-vitamin supplementation exerts preventive effect on autism-like behavior and neurodevelopmental impairment in hippocampus of mice offspring gestationally exposed to PM2.5, to which alleviated mitochondrial damage, increased anti-inflammatory and antioxidant capacity and synaptic efficiency, reduced neuronal apoptosis and improved hippocampal neurogenesis may contribute.

Jonathan Rosand, MD, Ana-Maria Vranceanu, PhD
Review: Post-Intensive Care Syndrome: Unique Challenges in the Neurointensive Care Unit  
September 4, 2019
Within the last couple of decades, advances in critical care medicine have led to increased survival of critically ill patients, as well as the discovery of notable, long-term health challenges in patients and their loved ones. The terms post-intensive care syndrome (PICS) and PICS-family (PICS-F) have been used in non-neurocritical care populations to characterize the cognitive, psychiatric, and physical sequelae associated with critical care hospitalization in patients and their informal caregivers (e.g., family and friends who provide unpaid care). In this review, we first summarize the literature on the cognitive, psychiatric, and physical correlates of PICS and PICS-F in non-neurocritical patient populations and draw attention to their long-term negative health consequences.

Griciuc A, Patel S, Federico AN, Choi SH, Innes BJ, Oram MK, Cereghetti G, McGinty D, Anselmo A, Sadreyev RI, Hickman SE, El Khoury J, Colonna M, Tanzi RE.
TREM2 Acts Downstream of CD33 in Modulating Microglial Pathology in Alzheimer's Disease.
Sept.4, 2019
This study describes how to Alzheimer’s disease-associated genes regulate neuroninflammation in the brain.

Shaun Patel, PhD
Precision electronic medicine in the brain
September 2, 2019
Periodically throughout history developments from adjacent fields of science and technology reach a tipping point where together they produce unparalleled advances, such as the Allen Brain Atlas and the Human Genome Project. Today, research focused at the interface between the nervous system and electronics is not only leading to advances in fundamental neuroscience, but also unlocking the potential of implants capable of cellular-level therapeutic targeting. Ultimately, these personalized electronic therapies will provide new treatment modalities for neurodegenerative and neuropsychiatric illness; powerful control of prosthetics for restorative function in degenerative diseases, trauma and amputation; and even augmentation of human cognition. Overall, we believe that emerging advances in tissue-like electronics will enable minimally invasive devices capable of establishing a stable long-term cellular neural interface and providing long-term treatment for chronic neurological conditions.

Suh J, Romano DM, Nitschke L, Herrick SP, DiMarzio BA, Dzhala V, Bae JS, Oram MK, Zheng Y, Hooli B, Mullin K, Gennarino VA, Wasco W, Schmahmann JD, Albers MW, Zoghbi HY, Tanzi RE.
Loss of Ataxin-1 Potentiates Alzheimer's Pathogenesis by Elevating Cerebral BACE1 Transcription. 
Aug. 22, 2019
This paper shows that the gene responsible for spinal cerebellar ataxia, ATXN1, also contributes to Alzheimer’s  disease pathology by regulating the production of beta-amyoid in the brain.