A/Prof Nawaf Yassi, Lab Head | WEHI Researcher Profile

Q: SAMe – A Phase II Clinical Trial

S-adenosyl methionine (SAMe) is a natural compound which plays a key role in the homocysteine cycle. It is also a key substrate for multiple biochemical methylation pathways, including DNA methylation and methylation of PP2a, the primary tau phosphatase enzyme. Reduced methylation of PP2a has been shown to be associated with the development of Alzheimer’s disease pathology (particularly p-tau), and SAMe has been shown to attenuate this process in preclinical models.We are conducting a phase 2 trial using oral SAMe in patients will mild to moderate Alzheimer’s disease to investigate its effect on levels of p-tau in the disorder.SAMe could represent a simple, cheap and safe intervention for patients with Alzheimer’s disease and other tauopathies.

Q: Blood Biomarkers Supporting Diagnosis of Dementia

Dementia diagnosis is challenging. In Australia, the average time taken from the beginning of symptoms to a diagnosis of dementia is over 3 years, and this is longer in people living in regional or rural areas, or people from culturally and linguistically diverse backgrounds. Even when a diagnosis is made, there are cases where the diagnosis may be inaccurate due to overlap of clinical symptoms between different dementias, and due to a number of other medical and psychological conditions that can mimic dementia. Brain scans and spinal fluid analysis can help improve diagnosis but are costly, limited in terms of access, and invasive in some cases. The possibility of a blood test supporting dementia diagnosis would revolutionise diagnosis and care for patients with or at risk of the condition. In this study, we are implementing a blood-based diagnostic test for patients being assessed for dementia at the Royal Melbourne Hospital Cognitive, Dementia and Memory Service (CDAMS) Clinic. We will investigate the diagnostic accuracy of these blood tests, and their impact on clinician diagnostic confidence.

About

Our lab’s vision is to develop an interdisciplinary approach to dementia research and care.

Dementia is a complex condition that crosses a number of clinical and scientific disciplines. We understand that a strong, multifaceted approach is required to make a significant impact in dementia research. This includes having a long-term coordinated approach to research.

The focus of our lab is to:

Improve dementia diagnosis using novel and established biomarkers
Investigate midlife risk factors that may better inform prevention strategies
Establish and support dementia cohorts
Facilitate investigator-led clinical trials
Support and develop access to dementia research for regional and rural Australians
Investigate and address caregiver needs
Mentor the next generation of dementia clinical researchers

Education

Joint appointments

Grants and funding

Publications

Selected publications from A/Prof Nawaf Yassi

Bhalala OG, Beamish J, Eratne D, Summerell P, Porter T, Laws SM, Kang MJ, Huq AJ, Chiu W-H, Cadwallader C, Walterfang M, Farrand S, Evans AH, Kelso W, Churilov L, Watson R, Yassi N, Velakoulis D, Loi SM. Blood biomarker profiles in young-onset neurocognitive disorders: A cohort study.Australian & New Zealand Journal of Psychiatry. 2025;:10.1177/00048674241312805

Pavlin‐Premrl D, Waters M, Thijs V, Mitchell PJ, Yassi N, Parsons MW, Weir L, Pesavento L, Maingard J, Cloud G, Stanislaus V, Ngun M, Campbell BCV. Symptomatic Intracranial Atherosclerosis in an Australian Context: Common and Underdiagnosed in Multiple Ethnic Groups. Stroke Vascular and Interventional Neurology. 2025;5(1):10.1161/svin.124.001397

Wrigley S, Cody R, Amadoru S, Huynh A, Galante O, Mandrawa C, Yassi N, Yates P. Prevalence and associations of cerebral microbleeds in an Australian memory clinic cohort. Internal Medicine Journal. 2024;:10.1111/imj.16614

Yassi N, Yogendrakumar V, Churilov L, Meretoja A, Wu T, Campbell BCV, Strbian D, Jeng J-S, Woodhouse LJ, Ovesen C, Law ZK, Gu H-Q, Nie X, Liu J, Ma HH, Zhao H, Bath PM, Liu L, Sprigg N, Donnan GA, Davis SM. Tranexamic Acid Within 4.5 Hours of Intracerebral Hemorrhage With the CTA Spot Sign. Neurology. 2024;103(12):10.1212/wnl.0000000000210104

Eratne D, Kang MJY, Lewis C, Dang C, Malpas C, Ooi S, Brodtmann A, Darby D, Zetterberg H, Blennow K, Berk M, Dean O, Bousman C, Thomas N, Everall I, Pantelis C, Wannan C, Cicognola C, Hansson O, Janelidze S, Santillo AF, Velakoulis D, Group TMS. Plasma neurofilament light outperforms glial fibrillary acidic protein in differentiating behavioural variant frontotemporal dementia from primary psychiatric disorders. Journal of the Neurological Sciences. 2024;467:10.1016/j.jns.2024.123291

Kataike VM, Desmond PM, Steward C, Mitchell PJ, Davey C, Yassi N, Bivard A, Parsons MW, Campbell BCV, Ng F, Venkatraman V. Iron changes within infarct tissue in ischemic stroke patients after successful reperfusion quantified using QSM. Neuroradiology. 2024;66(12):10.1007/s00234-024-03444-6

Holper S, Loveland PM, Churilov L, Italiano D, Watson R, Yassi N. Blood astrocyte biomarkers in AD: a systematic review and meta‐analysis. Alzheimer’s & Dementia. 2024;20(Suppl 2):10.1002/alz.090544

Rosenich E, Pirotta S, Cummins H, Norfolk M, Da Costa G, Yassi N, Churilov L, Sinnott RO, Brodtmann A, Pase MP, Barton C, Bush AI, Maruff P, Ayton D, Lim YY, Group BR. Baseline demographic, risk and cognitive characteristics of the final randomized sample enrolled in a decentralised multi‐domain lifestyle intervention trial (BetterBrains) to delay cognitive decline. Alzheimer’s & Dementia. 2024;20(Suppl 7):10.1002/alz.090564

Bhalala OG, Beamish J, Summerell P, Porter T, Laws SM, Kang M, Huq A, Eratne D, Walterfang M, Farrand S, Evans AH, Kelso W, Watson R, Yassi N, Velakoulis D, Loi SM. Multi‐omic blood biomarkers and cognitive profiles discriminate causes of younger‐onset neurocognitive symptoms: a cohort study. Alzheimer’s & Dementia. 2024;20(Suppl 2):10.1002/alz.085786

Yogendrakumar V, Balabanski AH, Johns H, Churilov L, Parsons NK, Beharry J, Weir L, Yassi N, Zhao H, Warwick A, Coote S, Langenberg F, Branagan L, Siddiqi W, Bivard A, Campbell BCV, Donnan GA, Davis SM, Mutimer C, Barker J, Santos AD, Ng JL, Ng F, Yan B, Ma M, Wong J, Park A, Sharobeam A, Valente M, Williams C, Ho S, Scarff P, Beltrame C, Shin C, Thijs V, Fink J, Barber A, Lin L. Evaluating the Safety and Efficacy of Telemedicine Physician Assessments on a Mobile Stroke Unit: Protocol for a Prospective Open-Label Blinded End-Point Randomized Controlled Trial.Journal of the American Heart Association. 2024;13(21):10.1161/jaha.124.036856