Preface_2023_Neuroinflammation-in-Vascular-Dementia

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Preface
With technological advances, neurology is entering a new era. At the end of
the 1800s, Italian pathologist Camillo Golgi (1843�1926) discovered the sil-
ver staining method for histological studies of brain tissue. This ground-
breaking technique was used by Spanish neuroscientist Santiago Ramon y
Cajal (1852�1934) in his extensive studies on neurons and other brain cells,
which proved that brain cells were separate entities connected with each
other. Both scientists received the Nobel Prize in Physiology and Medicine
in 1906 for their distinguished work. Their innovations ushered in the period
of “descriptive neurology,” where detailed pathological reports of diseases
could be coupled with clinical symptoms to deepen our understanding of the
major neurological diseases. The next major technological advance came in
the 1970s with the discovery of an algorithm, which formed the foundation
of computed axial tomography (CT) scanning and magnetic resonance imag-
ing (MRI). The first MRI in a living subject was performed in 1977, and by
the 1980s, MRI was used routinely. Those of us who had completed training
in neurology at the end of the descriptive era were amazed by the images of
the living brain seen for the first time. Just as the silver staining technology
inspired new scientific discovery, advances in imaging revived interest in
pathology since the images needed to be confirmed.
Molecular biology, computers, and machine learning have brought us in
the current era of precision medicine. This new world will require a new set
of skills to navigate an unprecedented amount of data. No longer will the
neurologist’s pin and hammer be sufficient in clinical medicine, although
they will remain essential as the first stage of patient interaction. Also
needed will be the ability to interpret complex imaging data from CT, MRI,
and positron emission tomography (PET).
At the same time, rapid advances in the sensitivity of instruments used in
molecular studies are revealing pathological networks that form the basis for
novel therapies. Molecular biology can now reveal the biochemical processes
that are the basis for pathological changes seen under the microscope and in
radiological images. As we enter the new world of genomics and proteomics,
the large number of molecules involved will make it necessary to use com-
puters to decipher and interpret the results. While this phase will offer the
rewards of precision medicine, tailoring diagnoses and treatments to the vast
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array of information, it will be dependent on the continued growth of com-
puter power and statistical analysis.
This is the third book in a series that began with the publication of Brain
Fluids and Metabolism (Oxford University Press, 1990) and the collection,
taken as a whole in many ways, spans the evolution that has brought us to
the current exciting era of discoveries in our field. The idea for the first book
began in 1984 while I was on a sabbatical at King’s College in London with
Michael Bradbury, an expert on the physiology of the blood�brain barrier.
At that time, biological nuclear magnetic resonance (NMR) was in its
infancy, and I was able to attend a course at London University on the basics
of NMR in living systems. I wrote the book to introduce the new science of
NMR and expand the knowledge on the physiology of cerebrospinal fluid
(CSF). As I began to understand the new world of molecular biology, I
decided to write the second book entitled Molecular Physiology and
Metabolism of the Nervous System (Oxford Press, 2012). Around that time,
I discovered matrix metalloproteinases (MMPs) and their role in the proteo-
lytic disruption of the blood�brain barrier. The book incorporated concepts
of moleculular biology and new developments in neuroimaging.
This present book, grew out of the recognition of the importance of
inflammation to the molecular events in brains of patients with dementia.
My interest in dementia developed during my neurological training at Albert
Einstein College of Medicine under Drs. Robert Katzman and Robert Terry,
who were the first to point out the importance of Alzheimers’s disease.
Three years later, I joined the faculty at the University of New Mexico
(UNM), which had just purchased a CT scanner, and we put it to use after I
encountered a patient with dementia and trouble walking. His CT scan
showed extensive damage to the white matter. After his death, we obtained
an autopsy that showed a rarely reported form of pathology of the white mat-
ter due to vascular disease. This was the first autopsy confirmed case of
Binswanger’s disease diagnosed during life by CT, and it focused my career
toward mechanisms of white matter damage. I became an expert in a disease
few people had heard of. Fortunately, the discovery coincided with a huge
uptick in interest in white matter changes detected on MRI. I was able to
combine studies on the mechanisms of white matter injury with the discov-
ery of the presence of MMPs in the CSF of patients with Binswanger’s dis-
ease and other forms of white matter disease. Research in white matter
injury was beginning to interest NIH and in 2006 I received funding to open
a new pathway for the study of white matter in dementia. Ever since George
Glenner in 1984 discovered amyloid in the plaques stained with Golgi’s
method by Alois Alzheimer, all research in dementia centered on this pro-
tein, leaving little room for those interested in subcortical white matter as a
cause of dementia.
With the new information from imaging and pathology, a number of
other proteins besides amyloid were found to be accumulating in the brain
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and contributing to inflammation. Reseach in dementia shifted to include
other causes.
All three books drew on advances in technology that have helped to bet-
ter understand the mechanisms behind damage to brain cells, leading to
dementia, and all are anchored in clinical medicine. Nine years after joining
the faculty, I became chair of the neurology department at UNM and
throughout my research career, I have seen patients and taught medical stu-
dents and residents. My interest in precision medicine began before my neu-
rology residency as a graduate student in biomedical engineering at the
Technion-Israel Institute of Technology in Haifa, Israel, where I studied con-
trol theory and computer diagnosis. However, the primitive nature of the
early computers drove me back to the clinical world. Working in many dif-
ferent roles in the hospital and the laboratory has made me aware of the
importance of teams with a wide variety of skills needed to augment patient
care.
Future teams will include clinicians, neuroradiologists, molecular biolo-
gists, computer scientists, and experts in analysis of large datasets. The hope
with all this effort by many people is that new treatments will evolve for the
diseases causing dementia.
Gary A. Rosenberg, MD
Albuquerque, New Mexico
September 2022
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