Dataset Information

Modified amyloid variants in pathological subgroups of ?-amyloidosis.

ABSTRACT:

Objective

Amyloid ? (A?) depositions in plaques and cerebral amyloid angiopathy (CAA) represent common features of Alzheimer's disease (AD). Sequential deposition of post-translationally modified A? in plaques characterizes distinct biochemical stages of A? maturation. However, the molecular composition of vascular A? deposits in CAA and its relation to plaques remain enigmatic.

Methods

Vascular and parenchymal deposits were immunohistochemically analyzed for pyroglutaminated and phosphorylated A? 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? in CAA resembled A? maturation in plaques and enabled the distinction of three biochemical stages of CAA. B-CAA stage 1 was characterized by deposition of A? in the absence of pyroglutaminated A?_N3pE and phosphorylated A?_pS8. B-CAA stage 2 showed additional A?_N3pE and B-CAA stage 3 additional A?_pS8. Based on the A? maturation staging in CAA and plaques, three case groups for A? pathology could be distinguished: group 1 with advanced A? maturation in CAA; group 2 with equal A? maturation in CAA and plaques; group 3 with advanced A? maturation in plaques. All symptomatic AD cases presented with end-stage plaque maturation, whereas CAA could exhibit immature A? deposits. Notably, A? pathology group 1 was associated with arterial hypertension, and group 2 with the development of dementia.

Interpretation

Balance of A? maturation in CAA and plaques defines distinct pathological subgroups of ?-amyloidosis. The association of CAA-related A? maturation with cognitive decline, the individual contribution of CAA and plaque pathology to the development of dementia within the defined A? pathology subgroups, and the subgroup-related association with arterial hypertension should be considered for differential diagnosis and therapeutic intervention.

SUBMITTER: Gerth J

PROVIDER: S-EPMC6043770 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Publications

Modified amyloid variants in pathological subgroups of <i>β</i>-amyloidosis.

Gerth Janina J Kumar Sathish S Rijal Upadhaya Ajeet A Ghebremedhin Estifanos E von Arnim Christine A F CAF Thal Dietmar R DR Walter Jochen J

Annals of clinical and translational neurology 20180606 7

<h4>Objective</h4>Amyloid <i>β</i> (A<i>β</i>) depositions in plaques and cerebral amyloid angiopathy (CAA) represent common features of Alzheimer's disease (AD). Sequential deposition of post-translationally modified A<i>β</i> in plaques characterizes distinct biochemical stages of A<i>β</i> maturation. However, the molecular composition of vascular A<i>β</i> deposits in CAA and its relation to plaques remain enigmatic.<h4>Methods</h4>Vascular and parenchymal deposits were immunohistochemically ...[more]

PMID: 30009199

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