Anne Cataldo, 57, Autophagy Researcher Known for Generous Collegiality
20 April 2009. It is with deep sadness that we inform the Alzheimer research community of the passing of Anne Cataldo, who directed the Laboratories for Molecular Neuropathology at McLean Hospital, Belmont, Massachusetts. Cataldo died on April 13 at University of Massachusetts Medical Center after a month of struggle with sudden complications from a blood immune disorder, according to a McLean administrator. “I have been friends with Anne for almost 20 years, but her death came as a total shock,” said Stephen Vincent of Athena Diagnostics, Inc.
Alzforum readers know Cataldo from her research on the cell biology of Alzheimer disease and Down syndrome. Cataldo was one of the first scientists to observe dysregulation of neuronal autophagy and lysosomal protein degradation in these diseases (Cataldo et al., 1994). She published on this topic early on with her husband, Peter Paskevich, as a co-author (Cataldo et al., 1996). Cataldo continued to advance this line of research in extended collaborations with her former postdoctoral adviser Ralph Nixon at the Nathan S. Kline Institute, Orangeburg, New York.
With her autophagy research, Cataldo leaves a lasting scientific legacy because this research topic is beginning to flourish widely in the field (e.g., Jaeger and Wyss-Coray, 2009) just as Cataldo herself had to end her life’s work; 40 of the topic’s 51 papers in AD were published since 2005. Cataldo also studied the effects of presenilin mutations in familial AD (Cataldo et al., 2004) and, more recently, APP signaling (see ARF conference story; Chen et al., 2006; Laifenfeld et al., 2007).
“Dr. Cataldo will not only be remembered for her originality, technical skill, and accomplishments as an investigator, but also for her enthusiasm, warmth, and creativity,” wrote Scott Rauch, president of McLean, in an e-mail announcement.
At Alzforum, Cataldo served on the Scientific Advisory Board in 2006 and as a friendly source to its reporters and editors. Beyond those who knew her personally, many scientists will remember Cataldo from her plenary lecture at the 2004 ICAD conference in Philadelphia, Pennsylvania. Cataldo is survived by her mother, her husband, two siblings, and two stepchildren, among other family. For more detail, see obituary. The Alzforum editors invite all who knew Anne to pay tribute to her life or share a memory via the comment box on this page.—Gabrielle Strobel.
News just reached me this morning of Anne's passing, through this forum.
I worked with Anne, and her future husband Pete, way back when we were just kids in Randy Nixon's lab. She was such a joy and so wonderful to work with. She sent a Christmas card to me every year. I had just visited McLean a few months ago, and Pete brought me to her lab during a tour of the place. I hadn't seen her in so many years, and she was just as bright and energetic and wonderful as over 20 years ago.
The world is less without her. My heart goes out to Pete.
University of Arkansas for Medical Sciences
This is a staggering loss to our AD research family. The importance of Anne's work is exceeded only by the warmth of her collegial disposition. She will be missed dearly by the research community, replete with friends and collaborators whose lives and careers Anne enriched.
Philadelphia College of Osteopathic Medicine
I was shocked and deeply saddened to hear of Anne's death.
Anne and I were graduate students in the same laboratory at the University of Maryland School of Medicine in Baltimore during the early and mid 1980’s. Annie, as I affectionately called her, was one of the first people that I met upon entering the Department of Pathology and Laboratory Medicine and we quickly became friends. We both were students in the neuropathology lab of Richard Broadwell and worked on projects addressing the cellular biology of the blood-brain barrier. Annie was already in the lab when I first started. She quickly took me under her wing and instructed me on the different histochemical, cytochemical and ultrastructural techniques that she was performing. This is when I realized that Annie was a great teacher, having the characteristics of commitment, patience and humility.
She also was a great friend. Annie would do anything for anyone in need and she really cared about others’ feelings. Our graduate school days were filled with worries about experiments, getting posters and grants finished on time, and about writing manuscripts that wouldn’t come back entirely in red from our advisor. Having Annie there certainly made it more fun and worthwhile. She was always the calming presence in our usual state of controlled chaos. There were times during which we would just stop and look at each other and break out laughing, she truly had the knack for keeping everything in perspective.
After graduate school, we both went on to postdoctoral fellowships that led us to Alzheimer disease research. Interestingly, the directions we took were definitely not mainstream, but rather a reflection of taking a more unorthodox approach to the problem. Annie was very creative and technically skilled even from her graduate school days, and her contemporary work on endosomal and lysosomal protein processing in AD certainly reflected that well. She and I often discussed her work at various scientific conferences as her work was a revolutionizing force in how we started thinking about the lysosomal system and autophagy in neurodegenerative disease. Annie had great scientific acumen that was readily apparent in discussions with her about her work. She was always enthusiastic and generous with her time for others.
Her legacy goes well beyond her accomplishments as she was not only a fabulous scientist, but also a wonderful colleague and friend. I feel blessed to have known Annie Cataldo, and I, like so many others, will miss her dearly.
New York University School of Medicine/Nathan Kline Institute
“One of the kindest colleagues I ever had” wrote a friend of mine today upon learning of Anne’s untimely passing. If you were lucky enough to collaborate with Anne, you soon came to know that her unique kindness, humor, and dedication to the relationship always went hand in hand with her passion for moving science forward creatively. How lucky it was, then, for me to enjoy a scientific partnership with Anne that spanned 25 years and continually brought pleasant surprises about the broader significance of lysosomal system pathology in Alzheimer disease described by Anne in the early days of protease research.
Anne’s explorations of vesicular trafficking began as a graduate student in Richard Broadwell’s laboratory. There, her meticulous studies of osmotic challenge in the brain provided insights about how stressed neurons mobilize ER and lysosomal pathways, which she would later bring to bear on her AD research. Our mutual interests led Anne to come to McLean Hospital for postdoctoral training and to study why cathepsins, which are normally localized to lysosomes within cells, were so abundant extracellularly in senile plaques. Nearly 50 publications later, the picture has clarified considerably, revealing disturbances in both endocytic and autophagic pathways to the lysosome, each of which can be tied closely to the major genetic and environmental risk factors for AD.
Tracing the extracellular cathepsin in AD first to a robustly mobilized neuronal lysosome system, Anne further sleuthed upstream of this lysosomal response, revealing disease-specific abnormalities of neuronal endosomes that precede other known AD-related neuropathologies. In studies published last year, she showed that the characteristic enlargement of endosomes in Down syndrome, which begins decades before AD onset, reflects a robust rab5-mediated acceleration of endocytosis that not only mobilizes the lysosome system but contributes to its dysfunction (Cataldo, 2008). In the intervening years between these observations, Anne’s work established clear pathogenic relevance of the endocytic dysfunction by showing its dependence on the extra copy of APP in a Down syndrome animal model. Recent studies by Bill Mobley’s group further linked this APP-driven endosome dysfunction to the degeneration of forebrain cholinergic neurons through a failure of endosome-mediated neurotrophin signaling. The collaborations of Rachael Neve’s group with Anne provided additional clues about molecular components linking high APP expression and mutant APP to endosome dysfunction and to further adverse cellular consequences of deranged endosomal signaling.
Anne’s findings on endocytosis and the many emerging directions of research on autophagy in AD that have developed from her early investigations of the lysosomal system continue to gain relevance as an important path toward understanding AD pathogenesis. They increasingly inform the work of a growing number of scientists who are now investigating the consequences of disturbed endocytic and autophagic function, not only in relation to neurodegeneration in the β-amyloidoses but in other dementias and neurodegenerative disorders. Anne’s interests in recent years were beginning to turn more translational to include the use of stem cells and other cellular vehicles to deliver trophic factors and other homeostatic agents to compromised neurons in vivo. These many research avenues will continue in the labs of her collaborators and beyond.
As important and enduring as these scientific contributions are, colleagues of Anne will agree that she placed the relationships in a collaboration above the science. She regularly traded personal time, comfort, and gain to offer help and advice, not just scientific, to collaborators and staff, which was always seasoned with her signature humor and self-effacing manner. Whether she was setting out before dawn from Boston to New York to get in a full day of discussions with NKI collaborators, or delaying the long return drive so that she could spend more time trouble-shooting problems with colleagues, Anne continually redefined the extremes of commitment and dedication to friends, even as medical problems intervened that would have slowed most others. Recognizing her technical savvy, many in the worldwide AD community also became beneficiaries of her generosity in sharing skills and wisdom. Everyone who spent time with Anne thought that they had a special relationship with her.
Anne leaves us a legacy of assuredly important scientific contributions and a second legacy of a large family of scientists who have shared the gift of knowing this beautiful person and will always feel blessed.
Cataldo AM, Mathews PM, Boiteau AB, Hassinger LC, Peterhoff CM, Jiang Y, Mullaney K, Neve RL, Gruenberg J, Nixon RA. Down syndrome fibroblast model of Alzheimer-related endosome pathology: accelerated endocytosis promotes late endocytic defects. Am J Pathol. 2008 Aug;173(2):370-84. PubMed.
Banner Research Institute
Anne represented an ideal scientist and person. Scientifically, her major contribution is her imaginative work on autophagy and lysosome systems in Alzheimer disease—work that was initiated decades before these became hot topics. Anne represented an optimal balance between being an outstanding scientist and a warm and open human being. She is sorely missed.
Nathan Kline Institute/NYU Langone School of Medicine
I am deeply saddened by the untimely passing of Anne. She was a friend and collaborator, with a calm and caring demeanor and a great sense of humor. Anne was tremendously generous with her resources, always willing to share reagents and experimental data to support ongoing studies. Most of all, Anne was tremendously generous with her time. She literally spent hours of her own valuable percentage of effort helping out her friends and colleagues, as well as helping to train and support postdoctoral fellows and graduate students. She was as adept at the microscope taking digital images of basal forebrain cholinergic neurons in mouse models of Down syndrome as she was evaluating biochemical measures of endosome enlargement in fibroblasts transfected with viral vectors.
Her tireless work ethic and contributions to the field of endosomal, autophagic, and lysosomal systems (EALS) pathology in Alzheimer disease and Down syndrome are irreplaceable. Anne also left the funniest voice messages, and I truly wish I could listen to all of them that I have received throughout the years over and over again. Anne will be sorely missed, but her memory lives on in the hearts and minds of her family, friends, and collaborators.