Gender	Male
E-mail	patrick.hof@mssm.edu
Education and Training	M.D., University of Geneva School of Medicine
	Postdoctoral Fellowship, The Scripps Research Institute

Dr. Hof is the Regenstreif Professor of Neuroscience and Vice-Chair for Translational Neuroscience of the Department of Neuroscience. In the Department, Dr. Hof also leads the Kastor Neurobiology of Aging Laboratories. His laboratory has extensive expertise in the pathology of neuropsychiatric disorders and has established an international reputation in quantitative approaches to neuroanatomy and studies of brain evolution.

Websites

    * Department of Neuroscience
    * Computational Neurobiology and Imaging Center
    * Advanced Imaging Program

Laboratory of Neuromorphology

Education and Training	M.D., University of Geneva School of Medicine
	Postdoctoral Fellowship, The Scripps Research Institute

Specific Clinical/Research Interest:
Experimental neuropathology, neurodegenerative disorders, brain aging; Functional anatomy of the cerebral cortex, comparative neuroanatomy; Computer-assisted morphometry, stereology, microscopy; Magnetic resonance microscopy, functional brain imaging

Current Students: PhD: Afia Akram NEU; PhD: Camilla Butti (exchange student); PhD: Steven Stockton NEU

Postdoctoral Fellows: Dara Dickstein, PhD (Instructor); Malin Hoistad, PhD

Research Personnel: Bridget Wicinski, Douglas Ehlenberger

Summary of Research Studies:
Our research is directed towards the study of selective neuronal vulnerability in dementing illnesses using classical neuropathological as well as modern quantitative immunohistochemical methods. We intend to develop a quantitative, detailed and cohesive definition of neuronal susceptibility to degeneration in the cerebral cortex, by extending data on Alzheimer disease to other dementing disorders as well as animal models of age-related illnesses, and by defining the key neurochemical and morphological characteristics linked to relative vulnerability (or resistance to degeneration) of identified neuronal populations. The regional and laminar distribution in the cerebral cortex of specific neuronal populations is investigated in a variety of neurodegenerative disorders, and quantitatively compared to Alzheimer disease and control brains. In addition, a detailed study of brains from aged patients with no records of neurological and psychiatric disorders is performed in order ! to define further the limits of normal aging in the brain. We also investigate transgenic mouse models, expressing the human tau gene or mutations in the amyloid precursor protein. We study spatial and temporal relationships between neuronal integrity and reflections of degeneration such as tangle formation, amyloid deposition and microvascular damage. We employ high field magnetic resonance microscopy, stereologic, and mathematical modeling approaches to develop an accurate quantitative appraisal of such pathological changes in a region- and layer-specific manner. Neuronal morphology is assessed in a quantitative manner using intracellular injection of hippocampal and neocortical neurons coupled with computerized reconstruction to assess the degree to which the accumulation of pathologic markers causes dendritic atrophy and spine loss in different subtypes of neocortical pyramidal cells. Such correlations of quantitative anatomical analyses and clinical data will be valuable to determine the causes and mechanisms of dementia and aging-related pathologies of the central nervous system. Altogether our research efforts will provide a quantitative assessment, in dementia cases of different severity and in relevant animal models, of the relative contribution of age-related vascular alterations, neuritic pathology and amyloid deposition to the progressive demise of selectively vulnerable neuronal subsets subserving cortical circuits critical for memory and cognition. The characterization of such vulnerable neurons and circuits is fundamental to the design of therapeutic strategies aiming at their protection or rescue. A recent project on myelination patterns and neuronal integrity in schizophrenia uses similar approaches. Finally we are investigating mammalian brain evolution with a focus on cetaceans and great apes. These studies have led us to identify specific neuronal types in parts of the cerebral cortex known to be involved in social awareness, judgement, and attention, that can be considered as markers of adaptive mechanisms and functions in response to particular ecological pressure.

Visit Dr. Patrick Hof's Laboratory of Neuromorphology for more information.

Akram A, Christoffel D, Rocher AB, Bouras C, Kovari E, Perl DP, Morrison JH, Herrmann FR, Haroutunian V, Giannakopoulos P, Hof PR. Stereologic estimates of total spinophilin-immunoreactive spine numbers in area 9 and the CA1 field: relationship with the progression of Alzheimer's disease. . Neurobiol. Aging 2008; 29: 1296-1307.

Rodriguez A, Ehlenberger DB, Dickstein DL, Hof PR, Wearne SL. Automated three-dimensional detection and classification of dendritic spines from fluorescence microscopy. Public Lib. Sci. One 2008; 3(4 )-e1997.

Radley JJ, Rocher AB, Rodriguez A, Ehlenberger DB, Dammann M, McEwen BS, Morrison JH, Wearne SL, Hof PR. Repeated stress alters dendritic spine morphology in the rat medial prefrontal cortex. J. Comp. Neurol 2008; 507: 1141-1150.

Mus E, Hof PR, Tiedge H. Dendritic BC200 RNA in aging and in Alzheimer's disease.. Proc. Natl. Acad. Sci. USA 2007; 104: 10679-10684.

Dickstein DL, Kabaso D, Rocher AB, Luebke JI, Wearne SL, Hof PR. Changes in the structural complexity of the aged brain. Aging Cell 2007; 6: 275-284.

Giannakopoulos P, Gold G, Kovari E, Imhof AB, Bouras C, Hof PR. Assessing the cognitive impact of Alzheimer disease pathology and vascular burden in the aging brain.. Acta Neuropathol. 2007; 113: 1-12.

Hof PR, Van der Gucht E. The structure of the cerebral cortex of the humpback whale, Megaptera novaeangliae (Cetacea, Mysticeti, Balaenopteridae). Anat. Rec 2007; 290: 1-31.

Rodriguez A, Ehlenberger DB, Hof PR, Wearne SL. Rayburst sampling, an algorithm for automated three-dimensional shape analysis from laser scanning microscopy images.. Nature Protocols 2006; 1: 2152-2161.

Hof PR, Morrison JH. The aging brain: morphomolecular senescence of cortical circuits. Trends Neurosci 2004; 27: 607-613.

Bussiere T, Giannakopoulos P, Bouras C, Perl DP, Morrison JH, Hof PR. Progressive degeneration of nonphosphorylated neurofilament protein-enriched pyramidal neurons predicts cognitive impairment in Alzheimer's disease: a stereologic analysis of prefrontal cortex area 9. J. Comp. Neurol 2003; 463: 281-302.