Neurology and psychiatry have been separated artificially by a divergence in their philosophical approaches, research and treatment methods. However the two fields are increasingly converging within the framework of modern neuroscience for the benefit of patients, many of whom straddle the two worlds. Historically, the foundation of modern neurology was cultivated early on by Freud in Paris under the supervision of Charcot, who trained as a neurologist, and endeavored to understand hysteria, acquiring experiences that set him on a trajectory for his life work. Freud became one of the most influential figures in psychiatry in the early 20th century focusing his work on psychoanalysis while silently a competing school of thought was emerging in Germany. Its star pupil, Alzheimer, was likewise a clinician with an interest in psychopathology. Being unable to find the pathological basis of dementia praecox, later terms schizophrenia, he turned his attention instead to the dementing disorder named in his honor. His original patient’s course, unique at the time, of a rapid deterioration in mental competence, was accompanied by paranoia, confusion, disorientation, severe memory loss, and language difficulty. Except for mental status, her neurological examination showed no deficit.
The severe loss of neurons in the brain and the presence of neurofibrillary tangles which seemed incidental to the psychiatric presentation, were as Alzheimer observed, very extensive. Only recently have the molecular changes of the protein fragment, β amyloid been appreciated as the cause of this prototypical neuropsychiatric illness. Later investigations into the molecular basis of Down’s syndrome, caused by an extra copy of genes on chromosome 21 (trisomy 21), that induced histopathological changes in the brain identical to those of Alzheimer’s disease, preceded the observation that up to 5% of Alzheimer’s disease patients appear early in life with a pattern of autosomal-dominant (AD) inheritance. β amyloid is now know to be a fragment of a large protein called amyloid precursor protein (APP).
More than 20 APP mutations that segregate with dementia have been described. While most Alzheimer’s disease families have no APP mutations, the genetic basis of Alzheimer disease advanced with the recognition of several other genetic loci encode early- or late-onset risk, respectively on chromosome 14q in the presenilin 1 protein and chromosome 1 in presenilin 2; and on chromosome 19q encoding at isoforms of apolipoprotein E (APOE; E4. APOE binds to the microtubule-associated protein tau which forms the paired helical filament and neurofibrillary tangles, and to the APP, amyloid beta peptide, a major component of the neuritic plaque. Identification of APOE in the cytoplasm of human neurons, and isoform-specific binding of APOE to the microtubule-associated protein tau, make it possible that APOE may affect microtubule function in the Alzheimer brain. The observation that the APO E4 allele is neither necessary nor sufficient for the expression of AD emphasizes the significance of other environmental or genetic factors that, either in conjunction with APOE4 or alone, increase the risk of Alzheimer disease. There are many other diseases that have garnished the benefit of a foundation in psychiatry and neurology including Tourette syndrome (TS) and pediatric autoimmune neuropsychiatric disorder associated with group A β hemolytic streptococcus infection (PANDAS) or PANS, due to other infectious triggers.
Readers interested in exploring this topic are recommended to a recent review by Martin