Andrea Slachevsky1,2,3,4, Leonardo Guzmán-Martínez5, Carolina Delgado6, Pablo Reyes1, Gonzalo A Farías5,6, Carlos Muñoz-Neira2, Eduardo Bravo7, Mauricio Farías7, Patricia Flores2,8, Cristian Garrido6, James T Becker9,10,11, Oscar L López9,10, Ricardo B Maccioni5,12. 1. Physiopathology Department, ICBM and East Neuroscience Department, Faculty of Medicine, Universidad de Chile, Santiago, Chile. 2. Cognitive Neurology and Dementia Unit, Neurological Sciences Department, Faculty of Medicine, Universidad de Chile and Neurology Department, Hospital del Salvador, Santiago, Chile. 3. Gerosciences Center for Brain Health and Metabolism, Santiago, Chile. 4. CIAE, Center for Advanced Research in Education, Universidad de Chile, Santiago, Chile. 5. International Center for Biomedicine, Santiago, Chile. 6. Neurology and Neurosurgery Department, Clinical Hospital, Universidad de Chile, Santiago, Chile. 7. Neuroradiology Department, Institute of Neurosurgery Asenjo, Santiago, Chile. 8. Neurology Unit, Department of Medicine, Clínica Alemana-Universidad del Desarollo, Santiago, Chile. 9. Department of Psychiatry, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA. 10. Department of Neurology, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA. 11. Department of Psychology, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA. 12. Faculty of Sciences, University of Chile, Santiago, Chile.
Abstract
BACKGROUND: Intracellular neurofibrillary tangles are part of the core pathology of Alzheimer's disease (AD), which are mainly composed of hyperphosphorylated tau protein. OBJECTIVES: The purpose of this study is to determine whether high molecular weight (HMW) or low molecular weight (LMW) tau protein levels, as well as the ratio HMW/LMW, present in platelets correlates with brain magnetic resonance imaging (MRI) structural changes in normal and cognitively impaired subjects. METHODS: We examined 53 AD patients and 37 cognitively normal subjects recruited from two Memory Clinics at the Universidad de Chile. Tau levels in platelets were determined by immunoreactivity and the MRI scans were analyzed using voxel-based morphometry in 41 AD patients. RESULTS: The HMW/LMW tau ratio was statistically different between controls and AD patients, and no associations were noted between HMW or LMW tau and MRI structures. In a multivariate analysis controlled for age and education level, the HMW/LMW tau ratio was associated with reduced volume in the left medial and right anterior cingulate gyri, right cerebellum, right thalamus (pulvinar), left frontal cortex, and right parahippocampal region. CONCLUSIONS: This exploratory study showed that HMW/LMW tau ratio is significantly higher in AD patients than control subjects, and that it is associated with specific brain regions atrophy. Determination of peripheral markers of AD pathology can help understanding the pathophysiology of neurodegeneration in AD.
BACKGROUND: Intracellular neurofibrillary tangles are part of the core pathology of Alzheimer's disease (AD), which are mainly composed of hyperphosphorylated tau protein. OBJECTIVES: The purpose of this study is to determine whether high molecular weight (HMW) or low molecular weight (LMW) tau protein levels, as well as the ratio HMW/LMW, present in platelets correlates with brain magnetic resonance imaging (MRI) structural changes in normal and cognitively impaired subjects. METHODS: We examined 53 ADpatients and 37 cognitively normal subjects recruited from two Memory Clinics at the Universidad de Chile. Tau levels in platelets were determined by immunoreactivity and the MRI scans were analyzed using voxel-based morphometry in 41 ADpatients. RESULTS: The HMW/LMW tau ratio was statistically different between controls and ADpatients, and no associations were noted between HMW or LMW tau and MRI structures. In a multivariate analysis controlled for age and education level, the HMW/LMW tau ratio was associated with reduced volume in the left medial and right anterior cingulate gyri, right cerebellum, right thalamus (pulvinar), left frontal cortex, and right parahippocampal region. CONCLUSIONS: This exploratory study showed that HMW/LMW tau ratio is significantly higher in ADpatients than control subjects, and that it is associated with specific brain regions atrophy. Determination of peripheral markers of AD pathology can help understanding the pathophysiology of neurodegeneration in AD.
Authors: Jaime Ramos-Cejudo; Andrew D Johnson; Alexa Beiser; Sudha Seshadri; Joel Salinas; Jeffrey S Berger; Nathanael R Fillmore; Nhan Do; Chunlei Zheng; Zanetta Kovbasyuk; Babak A Ardekani; Nunzio Pomara; Omonigho M Bubu; Ankit Parekh; Antonio Convit; Rebecca A Betensky; Thomas M Wisniewski; Ricardo S Osorio Journal: J Am Heart Assoc Date: 2022-04-26 Impact factor: 6.106
Authors: Silvia Fossati; Jaime Ramos Cejudo; Ludovic Debure; Elizabeth Pirraglia; Je Yeong Sone; Yi Li; Jingyun Chen; Tracy Butler; Henrik Zetterberg; Kaj Blennow; Mony J de Leon Journal: Alzheimers Dement (Amst) Date: 2019-06-28
Authors: José Luis Molinuevo; Scott Ayton; Richard Batrla; Martin M Bednar; Tobias Bittner; Jeffrey Cummings; Anne M Fagan; Harald Hampel; Michelle M Mielke; Alvydas Mikulskis; Sid O'Bryant; Philip Scheltens; Jeffrey Sevigny; Leslie M Shaw; Holly D Soares; Gary Tong; John Q Trojanowski; Henrik Zetterberg; Kaj Blennow Journal: Acta Neuropathol Date: 2018-11-28 Impact factor: 17.088