Alzheimers Dementia: Inherited dementia with decreased nuclear integrity of the locus coeruleus followed by increased tau aggregation

Alzheimer's disease (AD), the most common form of dementia, is neuropathologically defined as the accumulation of amyloid beta (Aβ) plaques and neurofibrillary tangles

Then, around age 50, tau appears in the brain cortex, followed by Aβ and tau accumulation in the neocortex around age 60

In older adults, including preclinical sporadic AD, with specialized magnetic resonance imaging (MRI) methods, LC integrity peaks and begins to decline at age 54, which is the time in life when cortical tau begins to appear

Individuals carrying mutations in presenilin-1 (PSEN1) are destined to develop autosomal dominant Alzheimer's disease (ADAD) in early adulthood

In ADAD, Aβ deposition predates cortical tau pathology by ≈10 to 15 years

Given that LC is the initial site of pre-entangled matter in AD, tau is closely related to cognition

With this, Heidi IL Jacobs et al.

They used MRI to correlate LC integrity with PET and recognition of Aβ and Tau in the largest known ancestry of PSEN1 E280A (Glu280Ala) mutation carriers and age-matched non-carrier family members living in Antioquia, Colombia.

A subset of these carriers also had follow-up imaging and cognitive data after an average of 2 years, enabling the assessment of whether LC integrity was consistent with changes in tau and to determine whether LC integrity might be useful in the search for early prognostic markers Hope

What they found: LC integrity in carriers began to decline at age 32 years, 12 years earlier than clinical onset, and 20 years earlier than sporadic AD

In addition, LC integrity was positively correlated with memory

These findings support LC integrity as a marker of preclinical ADAD disease progression