Sequence of A beta-protein deposition in the human medial temporal lobe

The deposition of A beta-protein (A beta) and the development of neurofibri llary changes are important histopathological hallmarks of Alzheimer diseas e (AD). In this study, the medial temporal lobe serves as a model for the c hanges in the anatomical distribution pattern of different types of A beta- deposits occurring in the course of AD, as well as for the relationship bet ween the development of A beta-deposition and that of neurofibrillary patho logy. In the first of 4 phases of beta-amyloidosis, diffuse non-neuritic pl aques are deposited in the basal temporal neocortex. The same plaque type a ppears in the second phase within the external entorhinal layers pre-beta a nd pre-gamma, and fleecy amyloid deposits occur in the internal entorhinal layers pri-alpha, pri-beta, pri-gamma. and in CA1. In the third phase, A be ta-deposits emerge in the molecular layer of the fascia dentata, and bandli ke A beta-deposits occur in the subpial portion of the molecular layer of b oth the entorhinal region and the temporal neocortex. In addition, confluen t lake-like A beta-deposits appear in the parvopyramidal layer of the presu bicular region. The fourth phase is characterized by diffuse and core-only plaques in CA4. Diffuse plaques evolve sporadically in the external entorhi nal layer pre-alpha. Parallel to the evolution of beta-amyloidosis as repre sented by the 4 phases, neuritic plaques gradually make their appearance in the temporal neocortex, entorhinal region, CAI, the molecular layer of the fascia dentata, and CA4. A prerequisite for their development is the prese nce of A beta and the presence of neurofibrillary tangles in neurons target ing the regions where neuritic plaques evolve. Each of the different types of A beta-deposits, including neuritic plaques, plays a specific role in th e distinct developmental sequence as represented by the 4 phases so that th e medial temporal lobe, inexorably becomes involved to an ever greater exte nt. The step-for-step involvement of connected anatomical subfields highlig hts the importance of the entorhino-hippocampal pathways for the expansion of beta-amyloidosis. The 4 phases in the evolution of beta-amyloidosis corr elate significantly with the stages of the neurofibrillary pathology propos ed by Braak and Braak.