Ageing-Related Neurodegeneration and Cognitive Decline

• Published in: International journal of molecular sciences Vol. 25; no. 7; p. 4065
• Main Authors: Alafuzoff, Irina, Libard, Sylwia
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.04.2024
• Subjects: ADNC; Adult; Age; Aged; Aged, 80 and over; ageing; Aging; alpha-synuclein; Alzheimer Disease; Alzheimer's disease; Amyloid beta-Peptides; amyloid beta-protein; ARTAG; Brain; Cognitive ability; Cognitive Dysfunction - etiology; Dementia; Females; Glycation End Products, Advanced; Humans; hyperphosphorylated-tau; LATE; LBD/PD; Lewy Body Disease; Limbic Encephalitis; Males; Middle Aged; Neurodegeneration; Neuropathology; PART; Pathology; Protein binding; Proteins; Synucleinopathies; Tauopathies; transactive DNA-binding protein 43; Sweden; transactive DNA-binding protein 43; ageing; ARTAG; LATE; ADNC; PART; LBD/PD; amyloid β-protein; hyperphosphorylated-τ; α-synuclein
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25074065

Neuropathological assessment was conducted on 1630 subjects, representing 5% of all the deceased that had been sent to the morgue of Uppsala University Hospital during a 15-year-long period. Among the 1630 subjects, 1610 were ≥41 years of age (range 41 to 102 years). Overall, hyperphosphorylated (HP) τ was observed in the brains of 98% of the 1610 subjects, and amyloid β-protein (Aβ) in the brains of 64%. The most common alteration observed was Alzheimer disease neuropathologic change (ADNC) (56%), followed by primary age-related tauopathy (PART) in 26% of the subjects. In 16% of the subjects, HPτ was limited to the locus coeruleus. In 14 subjects (<1%), no altered proteins were observed. In 3 subjects, only Aβ was observed, and in 17, HPτ was observed in a distribution other than that seen in ADNC/PART. The transactive DNA-binding protein 43 (TDP43) associated with limbic-predominant age-related TDP encephalopathy (LATE) was observed in 565 (35%) subjects and α-synuclein (αS) pathology, i.e., Lewy body disease (LBD) or multi system atrophy (MSA) was observed in the brains of 21% of the subjects. A total of 39% of subjects with ADNC, 59% of subjects with PART, and 81% of subjects with HPτ limited to the locus coeruleus lacked concomitant pathologies, i.e., LATE-NC or LBD-NC. Of the 293 (18% of the 1610 subjects) subjects with dementia, 81% exhibited a high or intermediate level of ADNC. In 84% of all individuals with dementia, various degrees of concomitant alterations were observed; i.e., MIXED-NC was a common cause of dementia. A high or intermediate level of PART was observed in 10 subjects with dementia (3%), i.e., tangle-predominant dementia. No subjects exhibited only vascular NC (VNC), but in 17 subjects, severe VNC might have contributed to cognitive decline. Age-related tau astrogliopathy (ARTAG) was observed in 37% of the 1610 subjects and in 53% of those with dementia.