Amyloid-β predominant Alzheimer's disease neuropathologic change

Abstract

Different subsets of Alzheimer's disease neuropathologic change (ADNC), including the intriguing set of individuals with severe/widespread amyloid-β (Aβ) plaques but no/mild tau tangles [Aβ-predominant (AP)-ADNC], may have distinct genetic and clinical features. Analysing National Alzheimer's Coordinating Center data, we stratified 1187 participants into AP-ADNC (n = 95), low Braak primary age-related tauopathy (PART; n = 185), typical-ADNC (n = 832) and high-Braak PART (n = 75). AP-ADNC differed in some clinical features and genetic polymorphisms in the APOE, SNX1, WNT3/MAPT and IGH genes. We conclude that AP-ADNC differs from classical ADNC with implications for in vivo studies.

Keywords: ADGC; NACC; amyloid-β; biomarker; diffuse plaques.

Figure 1

Conceptual summary of the spectrum of Alzheimer’s disease-related pathologies. Alzheimer’s disease (AD)-related pathologies include the presence of neurofibrillary tangles (NFTs) in six stages and the presence of amyloid-β (Aβ) plaques in five phases. Plotting these variables on a six-tiered disease progression scale also representing the NFT stages revealed major differences between typical AD neuropathologic change (NC), Aβ predominant ADNC (AP-ADNC) and primary age-related tauopathy (PART). These are associated with different in vivo biomarker patterns reflecting the Aβ amyloid (A) pathological Tau (T) and neurodegeneration (N) states. *In typical-ADNC, the highest NFT stage and Aβ phase is 6 and 5, respectively. **In AP-ADNC, the NFT stage does not increase beyond 2. ***In PART Aβ, phase does not increase beyond 1.