Alfons Maria Jakob was the son of a shopkeeper. He studied medicine in Munich, Berlin, and Strasbourg, where obtained his doctorate in 1908. In 1909 he commenced clinical work under the psychiatrist Emil Kraepelin and did laboratory work with Franz Nissl and Alois Alzheimer in Munich.
In 1911 he went to Hamburg to work with Theodor Kaes and became head of the laboratory of anatomical pathology at the psychiatric State Hospital Hamburg-Friedrichsberg. Following the death of Kaes in 1913, Jakob succeeded him as prosector. After serving in the German army in World War I, he returned to Hamburg and climbed the academic ladder. He was habilitated in neurology in 1919 and in 1924 became professor of neurology. Under Jakob's guidance the department grew rapidly. He made notable contributions to knowledge on concussion and secondary nerve degeneration and became a doyen of neuropathology.
Jakob published five monographs and more than 75 papers. His neuropathological studies contributed greatly to the delineation of several diseases, including multiple sclerosis and Friedreich's ataxia. He first recognised and described Alper's disease and Creutzfeldt-Jakob disease (the latter with Hans Gerhard Creutzfeldt). He accumulated immense experience in neurosyphilis, having a 200-bedded ward devoted exclusively to that disorder. Jakob made a lecture tour of the U.S.A. and South-America where he wrote a paper on the neuropathology of yellow fever.