Study finds lifelong neurogenesis in the hippocampus, but rates decline with age and, especially, Alzheimer’s disease

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Recent, imma­ture neu­rons (in red) and old­er, mature neu­rons (in blue) in the hip­pocam­pus of a 68-year-old’s brain. Cred­it: CSIC

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Old brains still make neu­rons, study finds, offer­ing a pos­si­ble way to pro­tect against Alzheimer’s (STAT):

“Reports of old brains’ decrepi­tude have been great­ly exag­ger­at­ed, sci­en­tists report­ed on Mon­day, unveil­ing results that con­tra­dict a much-dis­cussed 2018 study and instead sup­port the idea that human gray mat­ter is capa­ble of gen­er­at­ing new neu­rons up to the ninth decade of life.

The research, pub­lished in Nature Med­i­cine, also found that old brains from peo­ple with­out demen­tia have much high­er rates of such neu­ro­ge­n­e­sis than do the brains of peo­ple with Alzheimer’s dis­ease, offer­ing a new clue to a field that is des­per­ate for new ideas…

In a 43-year-old brain, for instance, the sci­en­tists mea­sured rough­ly 42,000 new neu­rons per cubic mil­lime­ter of hip­pocam­pus (approx­i­mate­ly the vol­ume of nine grains of table salt). An 87-year-old had 20,000 new neu­rons per cubic millimeter…

Although Llorens-Martín and her col­leagues did not have enough brains of the same age to make defin­i­tive com­par­isons of indi­vid­ual neu­ro­ge­n­e­sis rates, they saw hints of per­son-to-per­son vari­a­tion. Among peo­ple in their 60s with­out Alzheimer’s, she said, rates of neu­ro­ge­n­e­sis ranged from about 30,000 to 40,000 new neu­rons per cubic mil­lime­ter of hip­pocam­pus; in 80-some­things, it was 20,000 to 30,000.

“If you can increase the rate of neu­ro­ge­n­e­sis, it might be pro­tec­tive” against Alzheimer’s, she said.

The New Study:

Adult hip­pocam­pal neu­ro­ge­n­e­sis is abun­dant in neu­ro­log­i­cal­ly healthy sub­jects and drops sharply in patients with Alzheimer’s dis­ease (Nature Med­i­cine). From the abstract:

  • The hip­pocam­pus is one of the most affect­ed areas in Alzheimer’s dis­ease (AD) … By com­bin­ing human brain sam­ples obtained under tight­ly con­trolled con­di­tions and state-of-the-art tis­sue pro­cess­ing meth­ods, we iden­ti­fied thou­sands of imma­ture neu­rons in the DG of neu­ro­log­i­cal­ly healthy human sub­jects up to the ninth decade of life. These neu­rons exhib­it­ed vari­able degrees of mat­u­ra­tion along dif­fer­en­ti­a­tion stages of AHN (Note: adult hip­pocam­pal neu­ro­ge­n­e­sis). In sharp con­trast, the num­ber and mat­u­ra­tion of these neu­rons pro­gres­sive­ly declined as AD advanced. These results demon­strate the per­sis­tence of AHN dur­ing both phys­i­o­log­i­cal and patho­log­i­cal aging in humans and pro­vide evi­dence for impaired neu­ro­ge­n­e­sis as a poten­tial­ly rel­e­vant mech­a­nism under­ly­ing mem­o­ry deficits in AD that might be amenable to nov­el ther­a­peu­tic strategies.

The New Study in Context: