Modified amyloid variants in pathological subgroups of β‐amyloidosis. Issue 7 (6th June 2018)

• Record Type: Journal Article
• Authors: Gerth, Janina; Kumar, Sathish; Rijal Upadhaya, Ajeet; Ghebremedhin, Estifanos; von Arnim, Christine A. F.; Thal, Dietmar R.; Walter, Jochen
• Is Part Of: Annals of clinical and translational neurology. Volume 5:Issue 7(2018)
• Page Start: 815
• Page End: 831
• Publication Date: 2018-06-06
• Subjects: Nervous system -- Diseases -- Periodicals; Neurology -- Periodicals; 616.8005
• DOI: 10.1002/acn3.577
• Languages: English
• ISSNs: 2328-9503

Abstract

Abstract: Objective: Amyloid β (A β ) depositions in plaques and cerebral amyloid angiopathy (CAA) represent common features of Alzheimer's disease (AD). Sequential deposition of post‐translationally modified A β in plaques characterizes distinct biochemical stages of A β maturation. However, the molecular composition of vascular A β deposits in CAA and its relation to plaques remain enigmatic. Methods: Vascular and parenchymal deposits were immunohistochemically analyzed for pyroglutaminated and phosphorylated A β in the medial temporal and occipital lobe of 24 controls, 27 pathologically‐defined preclinical AD, and 20 symptomatic AD cases. Results: Sequential deposition of A β in CAA resembled A β maturation in plaques and enabled the distinction of three biochemical stages of CAA. B‐CAA stage 1 was characterized by deposition of A β in the absence of pyroglutaminated A β N3pE and phosphorylated A β pS8 . B‐CAA stage 2 showed additional A β N3pE and B‐CAA stage 3 additional A β pS8 . Based on the A β maturation staging in CAA and plaques, three case groups for A β pathology could be distinguished: group 1 with advanced A β maturation in CAA; group 2 with equal A β maturation in CAA and plaques; group 3 with advanced A β maturation in plaques. All symptomatic AD cases presented with end‐stage plaque maturation, whereas CAA could exhibit immature A β deposits. Notably, A β pathology group 1 was associated with arterial hypertension, and group 2 with the development of dementia. Interpretation: Balance of A β maturation in CAA and plaques defines distinct pathological subgroups of β ‐amyloidosis. The association of CAA‐related A β maturation with cognitive decline, the individual contribution of CAA and plaque pathology to the development of dementia within the defined A β pathology subgroups, and the subgroup‐related association with arterial hypertension should be considered for differential diagnosis and therapeutic intervention.