publications and development
My scientific vision is to cut across intellectual silos and integrate multiple streams of data to answer big questions in Alzheimer’s disease (AD) research. My research focus is to determine how aspects of brain connectivity could be developed as biomarkers of progression in AD. My current project is to derive patient-specific measures of resting-state functional connectivity based on individual cortical and tract anatomy.
My PhD thesis was focused on the interaction of neurovascular and neuronal damage in mouse models of AD. To date, increased amyloid-beta peptide, a cleavage product of the amyloid precursor protein (APP), has been advocated as the common mediator of both the neuronal and vascular damage incurred in AD. Recently, the thiazolidinedione pioglitazone was demonstrated to counter several pathological processes in the brains of aged amyloid-beta-overproducing APP transgenic mice. My PhD work showed that pioglitazone treatment commencing in young APP mice fully reversed cerebrovascular dysfunction and partially reversed cognitive impairment. However, pioglitazone failed to improve the attenuated cognitive task-induced neuroanatomical plasticity in the hippocampus that we reported for the first time in AD mice using magnetic resonance imaging methods. The vascular pathology appears to occur early in the disease process relative to amyloid-beta peptide deposition and cognitive deficits. Thus it is important to understand the molecular mechanisms of amyloid-beta-induced vascular pathology in AD and its reversal by candidate therapies, such as pioglitazone. To this end, I developed a new technique for the extraction of vascular protein from the mouse brain, compatible with two complementary mass spectrometry methods, to characterize the cerebrovascular proteome of normal (wild-type) mice. This approach allowed the identification of 6,630 proteins, mainly distributed in the endothelial and muscular compartments of the vascular wall. We found a few hundred proteins with significantly altered levels (upregulated or downregulated) in cerebral vessels of amyloid-beta-overproducing APP mice, including proteins related to vessel structure, vasomotricity and free radical production. Pioglitazone treatment exerted significant benefits in the APP mice, with over a third of the altered protein levels returned to wild-type levels. These results suggest that pioglitazone may be of benefit to AD patients with concurrent cerebrovascular deficits. In addition, some of the identified proteins could represent potential biomarkers for assessing the efficacy of therapies targeting cerebrovascular deficits in AD.
My MSc work was performed in the context of the Vervet Functional Genome Project, the goal of which was to (1) develop a well-characterized primate model for the study of primate genome rearrangements and evolution and (2) to improve the understanding of complex processes such as neuro-development and degeneration. Within the scope of this overall project, my focus was to study genome reorganization in the vervet monkey using both bioinformatics tools and laboratory protocols. Prior to my MSc, I worked at the Montreal Neurological Institute studying epilepsy genetics.
To summarize, my scientific approach is to integrate observations from in-vivo imaging with genomics, proteomics and bioinformatics in the study of AD and other neurodegenerative diseases, with the goal of discovering new therapeutic targets and improving methods to speed the drug discovery process.
Published Refereed Papers
- Badhwar A, Tam A, Dansereau C, Orban P, Toro R, Hoffstaedter F, Bellec P. Resting-state network dysfunction in Alzheimer’s disease: a systematic review and meta-analysis. Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring (in press)
- Lajoie I, Nugent S, Debacker C, Dyson K, Tancredi FB, Badhwar A, Belleville S, Deschaintre Y, Bellec P, Doyon J, Bocti C, Gauthier S, Arnold D, Kergoat MJ, Chertkow H, Monchi O, Hoge RD. Application of calibrated fMRI in Alzheimer’s disease. (submitted).
- Tam A, Dansereau C, Badhwar A, Orban P, Belleville S, Chertkow H, Dagher A, Hanganu A, Monchi O, Rosa-Neto P, Shmuel A, Breitner J, Bellec P.
A dataset of multiresolution functional brain parcellation in an elderly population with no or mild cognitive impairment.
Data in Brief 9:1122-1129, 2016.
- Badhwar A. Kennedy D, Poline JP, Toro R. Distributed collaboration: the case for the enhancement of Brainspell's interface. GigaScience (http://dx.doi.org/10.5524/100216), 2016.
- Badhwar A, Brown R, Stamimirovic D, Haqqani A, Hamel E.
Proteomic differences in brain vessels of Alzheimer’s disease mice: normalization by PPARγ agonist pioglitazone.
J Cereb Blood Flow Metab. 2016 Jun 23. pii: 0271678X16655172. [Epub ahead of print]
- Tam A, Dansereau C, Badhwar A, Orban P, Belleville S, Chertkow H, Dagher A, Hanganu A, Monchi O, Rosa-Neto P, Shmuel A, Wang S, Breitner J, Bellec P. Alzheimer’s Disease Neuroimaging Initiative.
Common Effects of Amnestic Mild Cognitive Impairment on Resting-State Connectivity Across Four Independent Studies.
Front Aging Neurosci. 24;7:242. doi: 10.3389/fnagi.2015.00242. eCollection 2015.
- Badhwar A, Stanimirovic DB, Hamel E, Haqqani AS.
The Proteome of mouse cerebral arteries.
J Cereb Blood Flow Metab. 34:1033-1046 2014 Mar 26.
- Badhwar A, Lerch JP, Hamel E, Sled JG.
Impaired structural correlates of memory in Alzheimer’s disease mice.
Neuroimage Clinical 3:290-300, 2013.
- Jansen A*, Sancak O*, D’Agostino MD*, Badhwar A, Roberts P, Gobbi G, Wilkinson R, Melanson D, Tampieri D, Koenekoop R, Gans M, Maat-Kievit A, Goedbloed M3, van den Ouweland AMW, Nellist M, Pandolfo M, McQueen M, Sims K, Thiele E, Dubeau F, Andermann F, Kwiatkowski DJ, Halley DJJ, Andermann E.
Unusually mild tuberous sclerosis phenotype is associated with TSC2 R905Q mutation.
Ann Neurol. 60(5):528-39, 2006. (* denotes equal contribution)
- Al-Asmi A, Jansen A*, Badhwar A*, Dubeau F, Tampieri D, Shustik C, Mercho S, Savard G, Dobson-Stone C, Monaco A, Andermann F, Andermann E.
Familial temporal lobe epilepsy as a presenting feature of chorea-acanthocytosis.
Epilepsia 46(8):1256-63, 2005. (* denotes equal contribution)
- Badhwar A, Jansen A, Andermann F, Pandolfo A, Andermann E.
Striking intrafamilial phenotypic variability and spastic paraplegia in the presence of similar homozygous expansions of the FRDA1 gene.
Mov Disord. 19(12):1424-31, 2004.
- Badhwar A, Berkovic SF, Dowling JP, Gonzales M, Narayanan S, Brodtmann A, Berzen L, Caviness J, Trenkwalder C, Winkelmann J, Rivest J, Lambert M, Hernandez-Cossio O, Carpenter S, Andermann F, Andermann E.
Action myoclonus-renal failure syndrome: characterization of a unique cerebro-renal disorder.
Brain 127(10):2173-82, 2004.
- Badhwar A, Siren A, Andermann E, Andermann F.
Myoclonic status epilepticus: video presentation.
Mov Disord. 17(2):409-11, 2002.
- Siegel AM, Andermann F, Badhwar A, Rouleau GA, Dam M, Hopf HC, Dichgans J, Sturzenegger M, Hopf NJ, Yasui N, Stepper F, Killer M, Vanneste JA, Acciarri N, Drigo P, Christensen J, Braun V, Konu D, Andermann E.
Anticipation in familial cavernous angioma: ascertainment bias or genetic cause.
Acta Neurol Scand. 98(6):372-6, 1998.
- Siegel AM, Andermann E, Badhwar A, Rouleau GA, Wolford GL, Andermann F, Hess.
Anticipation in familial cavernous angioma: a study of 52 families from International Familial Cavernous Angioma Study. IFCAS Group.
Lancet 352(9141):1676-7, 1998.
2016 Scalable Mouse Hippocampal atlas
2016 Brain Catalogue: House mouse
2015 Enhancement of Brainspell's interface
2014 Generated and made available to the scientific community the cerebrovascular proteomics database.
Badhwar A, Stanimirovic DB, Hamel E, Haqqani AS.
2013 Hippocampal Atlas of the J20 Mouse
- 2006 Vervet Monkey Genome Map - Sequences Submitted
- 44,506 sequences
Leveque G, Badhwar A, Nagy C, Forgetta V, McKee KH, Wasserscheid J and Dewar K
- 55,442 sequences
Leveque G, Badhwar A, Villeneuve A, Forgetta V, McKee KH, Wasserscheid J and Dewar K